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Why nature really chose phosphate

Published online by Cambridge University Press:  15 January 2013

Shina C. L. Kamerlin ,
Pankaz K. Sharma ,
Ram B. Prasad  and
Arieh Warshel
Shina C. L. Kamerlin
Affiliation:
Department of Cell and Molecular Biology (ICM), Uppsala Biomedical Centre, Uppsala University, Box 596, S-751 24 Uppsala, Sweden
Pankaz K. Sharma
Affiliation:
Department of Chemistry (SGM 418), University of Southern California, 3620 McClintock Avenue, Los Angeles, CA 90089, USA
Ram B. Prasad
Affiliation:
Department of Chemistry (SGM 418), University of Southern California, 3620 McClintock Avenue, Los Angeles, CA 90089, USA
Arieh Warshel*
Affiliation:
Department of Chemistry (SGM 418), University of Southern California, 3620 McClintock Avenue, Los Angeles, CA 90089, USA
*
*Author for correspondence: A. Warshel. Tel: (213) 740 4114; Email: [email protected]
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Abstract

Phosphoryl transfer plays key roles in signaling, energy transduction, protein synthesis, and maintaining the integrity of the genetic material. On the surface, it would appear to be a simple nucleophile displacement reaction. However, this simplicity is deceptive, as, even in aqueous solution, the low-lying d-orbitals on the phosphorus atom allow for eight distinct mechanistic possibilities, before even introducing the complexities of the enzyme catalyzed reactions. To further complicate matters, while powerful, traditional experimental techniques such as the use of linear free-energy relationships (LFER) or measuring isotope effects cannot make unique distinctions between different potential mechanisms. A quarter of a century has passed since Westheimer wrote his seminal review, ‘Why Nature Chose Phosphate’ (Science 235 (1987), 1173), and a lot has changed in the field since then. The present review revisits this biologically crucial issue, exploring both relevant enzymatic systems as well as the corresponding chemistry in aqueous solution, and demonstrating that the only way key questions in this field are likely to be resolved is through careful theoretical studies (which of course should be able to reproduce all relevant experimental data). Finally, we demonstrate that the reason that nature really chose phosphate is due to interplay between two counteracting effects: on the one hand, phosphates are negatively charged and the resulting charge-charge repulsion with the attacking nucleophile contributes to the very high barrier for hydrolysis, making phosphate esters among the most inert compounds known. However, biology is not only about reducing the barrier to unfavorable chemical reactions. That is, the same charge-charge repulsion that makes phosphate ester hydrolysis so unfavorable also makes it possible to regulate, by exploiting the electrostatics. This means that phosphate ester hydrolysis can not only be turned on, but also be turned off, by fine tuning the electrostatic environment and the present review demonstrates numerous examples where this is the case. Without this capacity for regulation, it would be impossible to have for instance a signaling or metabolic cascade, where the action of each participant is determined by the fine-tuned activity of the previous piece in the production line. This makes phosphate esters the ideal compounds to facilitate life as we know it.

Type
Review Article
Information
Quarterly Reviews of Biophysics , Volume 46 , Issue 1 , February 2013 , pp. 1 - 132
Copyright
Copyright © Cambridge University Press 2013

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References

7. References

Abrahams, J. P., Leslie, A. G. W., Lutter, R. & Walker, J. E. (1994). Structure at 2·8 Å resolution of F1-ATPase from bovine heart mitochondria. Nature 370, 621–628.CrossRefGoogle ScholarPubMed
Adachi, K., Oiwa, K., Nishizaka, T., Furuike, S., Noji, H., Itoh, H., Yoshida, M. & Kinosita, K. (2007). Coupling of rotation and catalysis in F1-ATPase revealed by single-molecule imaging and manipulation. Cell 130, 309–321.CrossRefGoogle ScholarPubMed
Adamczyk, A. J., Cao, J., Kamerlin, S. C. L. & Warshel, A. (2011). Catalysis by dihydrofolate reductase and other enzymes arises from electrostatic preorganization, not conformational motions. Proceedings of the National Academy of Sciences of the United States of America 108, 14115–14120.CrossRefGoogle Scholar
Adamczyk, A. J. & Warshel, A. (2011). Converting structural information into an allosteric-energy-based picture for elongation factor Tu activation by the ribosome. Proceedings of the National Academy of Sciences of the United States of America 108, 9827–9832.CrossRefGoogle ScholarPubMed
Adams, J. A. (2001). Kinetic and catalytic mechanisms of protein kinases. Chemical Reviews 101, 2271–2290.CrossRefGoogle ScholarPubMed
Admiraal, S. J. & Herschlag, D. (1995). Mapping of the transition state for ATP hydrolysis: implications for enzymatic catalysis. Chemistry & Biology 2, 729.CrossRefGoogle ScholarPubMed
Admiraal, S. J. & Herschlag, D. (2000). The substrate-assisted general base catalysis model for phosphate monoester hydrolysis: evaluation using reactivity comparisons. Journal of the American Chemical Society 122, 2145–2148.CrossRefGoogle Scholar
Agirrezabala, X. & Frank, J. (2009). Elongation in translation as a dynamic interaction among the ribosome, tRNA, and elongation factors EF-G and EF-Tu. Quarterly Reviews of Biophysics 42, 159–200.CrossRefGoogle ScholarPubMed
Aguilar-Pérez, F., Gómez-Tagle, P., Collado-Fregoso, E. & Yatsimirsky, A. K. (2006). Phosphate ester hydrolysis by hydroxo complexes of trivalent lanthanides stabilized by 4-imidazolecarboxylate. Inorganic Chemistry 45, 9502–9517.CrossRefGoogle ScholarPubMed
Ahmadian, M. R., Stege, P., Scheffzek, K. & Wittinghofer, A. (1997). Confirmation of the arginine-finger hypothesis for the GAP-stimulated GTP-hydrolysis reaction of Ras. Nature Structural Biology 4, 686–689.CrossRefGoogle ScholarPubMed
Ahn, J. W., Kraynov, V. S., Zhong, X. J., Werneburg, B. G. & Tsai, M. D. (1998). DNA polymerase β: effects of gapped DNA substrates on dNTP specificity, fidelity, processivity and conformational changes. The Biochemistry Journal 331, 79–87.CrossRefGoogle ScholarPubMed
Akola, J. & Jones, R. O. (2003). ATP hydrolysis in water – A density functional study. Journal of Physical Chemistry B 107, 11774–11783.CrossRefGoogle Scholar
Akola, J. & Jones, R. O. (2006). Density functional calculations of ATP systems. 2. ATP hydrolysis at the active site of actin. Journal of Physical Chemistry B 110, 8121–2129.CrossRefGoogle ScholarPubMed
Alberts, I. L., Wang, Y. & Schlick, T. (2007). DNA polymerase β catalysis: are different mechanisms possible? Journal of the American Chemical Society 129, 11100–11110.CrossRefGoogle ScholarPubMed
Alcolombri, U., Elias, M. & Tawfik, D. S. (2011). Directed evolution of sulfotransferases and paraoxonases by ancestral libraries. Journal of Molecular Biology 411, 837–853.CrossRefGoogle ScholarPubMed
Alhambra, C., Wu, L., Zhang, Z.-Y. & Gao, J. (1998). Walden-inversion-enforced transition-state stabilization in a protein tyrosine phosphatase. Journal of the American Chemical Society 120, 3858–3866.CrossRefGoogle Scholar
Alkherraz, A., Kamerlin, S. C. L., Feng, G., Sheikh, Q. I., Warshel, A. & Williams, N. H. (2010). Phosphate ester analogues as probes for understanding enzyme catalysed phosphoryl transfer. Faraday Discussions 145, 281–299.CrossRefGoogle Scholar
Allin, C., Ahmadian, M. R., Wittinghofer, A. & Gerwert, K. (2001). Monitoring the GAP catalyzed H-Ras GTPase reaction at atomic resolution in real time. Proceedings of the National Academy of Sciences of the United States of America 98, 7754–7759.CrossRefGoogle Scholar
Allin, C. & Gerwert, K. (2001). Ras catalyzes GTP hydrolysis by shifting negative charges from γ- to β-phosphate as revealed by time-resolved FTIR difference spectroscopy. Biochemistry 40, 3037–3046.CrossRefGoogle ScholarPubMed
Anderson, V. E., Cassano, A. G. & Harris, M. E. (2006). Isotope Effects in Chemistry and Biology. Boca Raton, FL: Taylor and Francis.Google Scholar
Åqvist, J. & Feierberg, I. (2002). The catalytic power of ketosteroid isomerase investigated by computer simulation. Biochemistry 41, 15728–15735.Google Scholar
Åqvist, J., Kolmodin, K., Florián, J. & Warshel, A. (1999). Mechanistic alternatives in phophsate monoester hydrolysis: what conclusions can be drawn from available experimental data? Chemistry & Biology 6, R71–R80.CrossRefGoogle ScholarPubMed
Åqvist, J. & Warshel, A. (1989). Calculations of free energy profiles for the staphylococcal nuclease catalyzed reaction. Biochemistry 28, 4680–4689.CrossRefGoogle ScholarPubMed
Åqvist, J. & Warshel, A. (1990). Free energy relationships in metalloenzyme-catalyzed reactions. Calculations of the effects of metal ion substitutions in staphylococcal nuclease. Journal of the American Chemical Society. 112, 2860–2868.CrossRefGoogle Scholar
Åqvist, J. & Warshel, A. (1993). Simulation of enzyme reactions using valence bond force fields and other hybrid quantum/classical approaches. Chemical Reviews 93, 2523–2544.CrossRefGoogle Scholar
Arantes, G. M. & Chaimovich, H. (2005). Thiolysis and alcoholysis of phosphate tri- and monoesters with alkyl and aryl leaving groups. An ab initio study in the gas phase. Journal of Physical Chemistry A 109, 5625–5635.CrossRefGoogle ScholarPubMed
Arndt, J. W., Gong, W. M., Zhong, X. J., Showalter, A. K., Liu, J., Dunlap, C. A., Lin, Z., Paxson, C., Tsai, M. D. & Chan, M. K. (2001). Insight into the catalytic mechanism of DNA polymerase β: structures of intermediate complexes. Biochemistry 40, 5368–5375.CrossRefGoogle ScholarPubMed
Arora, K., Beard, W. A., Wilson, S. H. & Schlick, T. (2005). Mismatch-induced conformational distortions in polymerase support an induced-fit mechanism for fidelity. Biochemistry 44, 13328–13341.CrossRefGoogle ScholarPubMed
Arora, K. & Schlick, T. (2004). In silico evidence for DNA polymerase-β’s substrate-induced conformational change. Biophysical Journal 87, 3088–3099.CrossRefGoogle ScholarPubMed
Atkins, P. W. (1998). Physical Chemistry, 6 edn, Oxford: Oxford University Press.Google Scholar
Averbuch-Pouchot, M. T. & Durif, A. (1996). Topics in Phosphate Chemistry, Singapore: World Scientific Publishing Co. Pte. Ltd.CrossRefGoogle Scholar
Ba-Saif, S. A., Davis, A. M. & Williams, A. (1989a). Effective charge distribution for attack of phenoxide ion on aryl methyl phosphate monoanion: studies related to the action of ribonuclease. The Journal of Organic Chemistry 54, 5483–5486.CrossRefGoogle Scholar
Ba-Saif, S. A., Davis, A. M. & Williams, A. J. (1989b). Effective charge distrtibution for attack of phenoxide ion on aryl methyl phosphate monoanion: studies related to the action of ribonuclease. The Journal of Organic Chemistry 54, 5483–5486.CrossRefGoogle Scholar
Ba-Saif, S. A., Waring, M. A. & Williams, A. (1990). Single transition states in the transfer of a neutral phosphoryl group between phenoxide ion nucleophiles in aqueous solution. Journal of the American Chemical Society. 112, 8115–8120.CrossRefGoogle Scholar
Ba-Saif, S. A., Waring, M. A. & Williams, A. (1991). Dependence of transition-state structure on nucleophile in the reaction of aryl oxide anions with aryl diphenylphosphate esters. Journal of the American Chemical Society Perkin Transactions 2, 1653–1659.CrossRefGoogle Scholar
Babtie, A. C., Bandyopadhyay, S., Olguin, L. F. & Hollfelder, F. (2009). Efficient catalytic promiscuity for chemically distinct reactions. Angewandte Chemie (International ed. in English) 48, 3692–3694.CrossRefGoogle ScholarPubMed
Bakhtina, M., Lee, S., Wang, Y., Dunlap, C., Lamarche, B. & Tsai, M.-D. (2005). Use of viscogens, dNTPαS, and Rhodium(III) as probes in stopped-flow experiments to obtain new evidence for the mechanism of catalysis by DNA polymerase β. Biochemistry 44, 5177–5187.CrossRefGoogle ScholarPubMed
Bao, Z. Q., Jacobsen, D. M. & Young, M. A. (2011). Briefly bound to active: transient binding of a second catalytic magnesium activates the structure and dynamics of CDK2 kinase for catalysis. Structure 19, 675–690.CrossRefGoogle ScholarPubMed
Barbacid, M. (1987). Ras Genes. Annual Review of Biochemistry 56, 779–827.CrossRefGoogle ScholarPubMed
Barbany, M., Gutierrez-De-teran, H., Sanz, F., Villà-Freixa, J. & Warshel, A. (2003). On the generation of catalytic antibodies by transition state analogues. ChemBioChem: A European Journal of Chemical Biology 4, 277–285.CrossRefGoogle ScholarPubMed
Barnard, P. W. C., Bunton, C. A., Llewellyn, D. R., Vernon, C. A. & Welch, V. A. (1961). The reactions of organic phosphates. Part V. The hydrolysis of triphenyl and trimethyl phosphates. Journal of the Chemical Society 2670–2676.CrossRefGoogle Scholar
Barnes, J. A., Wilkie, J. & Williams, I. H. (1994). Transition-state structural variation and mechanistic change. Journal of the Chemical Society Faraday Transactions 90, 1709–1714.CrossRefGoogle Scholar
Baxter, N. J., Olguin, L. F., Golicnick, M., Feng, G., Hounslow, A. M., Bermel, W., Blackburm, G. M., Hollfelder, F., Waltho, J. P. & Williams, N. H. (2006). A Trojan horse transition state analogue generated by MgF3- formation in an enzyme active site. Proceedings of the National Academy of Sciences of the United States of America 103, 14732–14737.CrossRefGoogle Scholar
Beard, W. A. & Wilson, S. H. (2003). Structural insights into the origins of DNA polymerase fidelity. Structure 11, 489–496.CrossRefGoogle ScholarPubMed
Beatty, R. (2001). The Elements: Phosphorus. New York: Marshall Cavendish Corporation.Google Scholar
Beke-Somfai, T., Feng, B. & Nordén, B. (2012). Energy phase shift as mechanism for catalysis. Chemical Physics Letters 535, 169–172.CrossRefGoogle Scholar
Beke-Somfai, T., Lincoln, P. & Norden, B. (2011). Double-lock ratchet mechanism revealing the role of αSER-344 in F0F1 ATP synthase. Proceedings of the National Academy of Sciences of the United States of America 108, 4828–4833.CrossRefGoogle Scholar
Benitez, B. A. S., Arora, K. & Schlick, T. (2006). In silico studies of the African swine fever virus DNA polymerase X support an induced-fit mechanism. Biophysical Journal 90, 42–56.CrossRefGoogle Scholar
Benkovic, S. J. & Hammes-Schiffer, S. (2003). A perspective on enzyme catalysis. Science 301, 1196–1202.CrossRefGoogle ScholarPubMed
Bennett, C. H. (1977). Molecular dynamics and transition state theory: the simulation of infrequent events. In Alogrithms for Chemical Computations, Americal Chemical Society, vol. 46 (Ed. Christofferson, R.), pp. 63–97. Washington, D.C.Google Scholar
Benson, S. W. (1965). Bond energies. Journal of Chemical Education 42, 502–518.CrossRefGoogle Scholar
Berg, J. M., Tymoczko, J. L. & Stryer, L. (2010). Biochemistry, 7th edn. New York: W. H. Freeman and Co.Google Scholar
Bilgin, N. & Ehrenberg, M. (1994). Mutations in 23-S ribosomal-RNA perturb transfer-RNA selection and can lead to streptomycin dependence. Journal of Molecular Biology 235, 813–824.CrossRefGoogle Scholar
Blackburn, G. M. & Williams, N. H. (2003). Comment on ‘The pentacovalent phosphorus intermediate of a phosphoryl transfer reaction’. Science 301, 1184.CrossRefGoogle ScholarPubMed
Blackburn, P. & Moore, S. (1982). Pancreatic ribonuclease. In The Enzymes, vol. 15 (Ed. Boyer, P. D.), pp. 317–433. New York: Academic Press.Google Scholar
Blaskovich, M. A. (2009). Drug discovery and protein tyrosine phosphatases. Current Medicinal Chemistry 16, 2095–2176.CrossRefGoogle ScholarPubMed
Bobyr, E., Lassila, J. K., Wiersma-Koch, H. I., Fenn, T. D., Lee, J. J., Nikolic-Hughes, I., Hodgson, K. O., Rees, D. C., Hedman, B. & Herschlag, D. (2012). High-resolution analysis of Zn(2+) coordination in the alkaline phosphatase superfamily by EXAFS and X-ray crystallography. Journal of Molecular Biology 415, 102–117.CrossRefGoogle ScholarPubMed
Bohm, A., Gaudet, R. & Sigler, P. B. (1997). Structural aspects of heterotrimeric G-protein signaling. Current Opinion in Biotechnology 8, 480–487.CrossRefGoogle ScholarPubMed
Bojin, M. D. & Schlick, T. (2007). A Quantum mechanical investigation of possible mechanisms for the nucleotidyl transfer reaction catalyzed by DNA polymerase β. Journal of Physical Chemistry B 111, 11244–11252.CrossRefGoogle ScholarPubMed
Bondar, A.-N., Fischer, S., Smith, J. C., Elstner, M. & Suhai, S. (2004a). Key role of electrostatic interactions in bacteriorhodopsin proton transfer. Journal of the American Chemical Society 126, 14668–14677.CrossRefGoogle ScholarPubMed
Bondar, A. N., Elstner, M., Suhai, S., Smith, J. C. & Fischer, S. (2004b). Mechanism of primary proton transfer in bacteriorhodopsin. Structure 12, 1281–1288.CrossRefGoogle ScholarPubMed
Borowiec, J. A., Dean, F. B., Bullock, P. A. & Hurwitz, J. (1990). Binding and unwinding—how T antigen engages the SV40 origin of DNA replication. Cell 60, 181–184.CrossRefGoogle ScholarPubMed
Bos, J. (1989). Ras oncogenes in human cancer: a review. Cancer Research 49, 4682–4689.Google ScholarPubMed
Bos, J. L., Rehmann, H. & Wittinghofer, A. (2007). GEFs and GAPs: critical elements in the control of small G proteins. Cell 129, 865–877.CrossRefGoogle ScholarPubMed
Bose-Basu, B., Derose, E. F., Kirby, T. W., Mueller, G. A., Beard, W. A., Wilson, S. H. & London, R. E. (2004). Dynamic characterization of a DNA repair enzyme: NMR studies of [methyl-C-13]methionine-labeled DNA polymerase β. Biochemistry 43, 8911–8922.CrossRefGoogle ScholarPubMed
Bourne, H. R., Sanders, D. A. & Mccormick, F. (1991). The GTPase superfamily: conserved structure and molecular mechanism. Nature 349, 117–127.CrossRefGoogle ScholarPubMed
Bourne, N. & Williams, A. (1984). Effective charge on oxygen in phosphoryl (-PO32−) group transfer from an oxygen donor. The Journal of Organic Chemistry 49, 1200–1204.CrossRefGoogle Scholar
Bowtell, D., Fu, P., Simon, M. & Senior, P. (1992). Identification of murine homologues of the drosophila son of sevenless gene. Potential activators of ras. Proceedings of the National Academy of Sciences of the United States of America 89, 6511–6515.CrossRefGoogle ScholarPubMed
Boyer, P. D. (1993). The binding change mechanism for ATP synthase – some probabilities and possibilities. Biochimica et Biophysica Acta 1140, 215–250.CrossRefGoogle ScholarPubMed
Boyer, P. D. (1997). The ATP synthase – a splendid molecular machine. Annual Review of Biochemistry 66, 717–749.CrossRefGoogle ScholarPubMed
Branduardi, D., De Vivo, M., Rega, N., Barone, V. & Cavalli, A. (2011). Methyl phosphate dianion hydrolysis in solution characterized by path collective variables coupled with DFT-based enhanced sampling simulations. Journal of Chemical Theory and Computation 7, 539–543.CrossRefGoogle ScholarPubMed
Braun-Sand, S., Sharma, P. K., Tchu, Z., Pisliakov, A. V. & Warshel, A. (2008). The energetics of the primary proton transfer in bacteriorhodopsin revisited: it is a sequential light-induced charge separation after all. Biochimica et Biophysica Acta 1777, 441–452.CrossRefGoogle Scholar
Braun-Sand, S., Strajbl, M. & Warshel, A. (2004). Studies of proton translocations in biological systems: simulating proton transport in carbonic anhydrase by EVB based models. Biophysical Journal 87, 2221–2239.CrossRefGoogle ScholarPubMed
Broek, D., Toda, T., Michaeli, T., Levin, L., Birchmeier, C., Zoller, M., Powers, S. & Wigler, M. (1987). The S. cerevisiae CDC25 gene product regulates the RAS/adenylate cyclase pathway. Cell 48, 789–799.CrossRefGoogle Scholar
Bruice, T. C., Tsubouchi, A., Dempcy, R. O. & Olson, L. P. (1996). One- and two-metal ion catalysis of the hydrolysis of adenosine 3′-alkyl phosphate esters. Models for one- and two-metal ion catalysis of RNA hydrolysis. Journal of the American Chemical Society 118, 9867–9875.CrossRefGoogle Scholar
Buchwald, S. L., Friedman, J. M. & Knowles, J. R. (1984). Stereochemistry of nucleophilic displacement on two phosphoric monoesters and a phosphoguanidine: the role of metaphosphate. Journal of the American Chemical Society 106, 4911–4916.CrossRefGoogle Scholar
Bunton, C. A., Llewwellyn, D. R., Oldham, K. G. & Vernon, C. A. (1958). The reaction of organic phosphates. Part I. The hydrolysis of methyl dihydrogen phosphate. Journal of the Chemical Society 3574–3587.CrossRefGoogle Scholar
Bunton, C. A., Mhala, M. M., Oldham, K. G. & Vernon, C. A. (1960). The reactions of organic phosphates. Part II. The hydrolysis of dimethyl phosphate. Journal of the Chemical Society 3293–3301.CrossRefGoogle Scholar
Butcher, W. W. & Westheimer, F. (1955). The lanthanum hydroxide gel promoted hydrolysis of phosphate esters. Journal of the American Chemical Society 77, 2420–2424.CrossRefGoogle Scholar
Cardone, M. H., Roy, N., Stennicke, H. R., Salvesen, G. S., Franke, T. F., Stanbridge, E., Frisch, S. & Reed, J. C. (1998). Regulation of cell death protease caspase-9 by phosphorylation. Science 282, 1318–1321.CrossRefGoogle ScholarPubMed
Carpenter, B. K. (2005). Nonstatistical dynamics in thermal reactions of polyatomic molecules. Annual Review of Physical Chemistry 56, 57–89.CrossRefGoogle ScholarPubMed
Cassano, A. G., Anderson, V. E. & Harris, M. E. (2002). Evidence for direct attack by hydroxide in phosphodiester hydrolysis. Journal of the American Chemical Society 124, 10964–10965.CrossRefGoogle ScholarPubMed
Catrina, I., O'Brien, P. J., Purcell, J., Nikolic-Hughes, I., Zalatan, J. G., Hengge, A. C. & Herschlag, D. (2007). Probing the origin of the compromised catalysis of E. coli alkaline phosphatase in its promiscuous sulfatase reaction. Journal of the American Chemical Society 129, 5760–5765.CrossRefGoogle ScholarPubMed
Cavalli, A. & Carloni, P. (2002). Enzymatic GTP Hydrolysis: insights from an ab initio molecular dynamics study. Journal of the American Chemical Society 124, 3763–3768.CrossRefGoogle ScholarPubMed
Cavalli, A., De Vivo, M. & Recanatini, M. (2003). Density functional study of the enzymatic reaction catalyzed by a cyclin-dependent kinase. Chemical Communications (Cambridge, England) 7, 1308–1309.CrossRefGoogle Scholar
Chakrabarti, P. P., Daumke, O., Suveyzdis, Y., Kotting, C., Gerwert, K. & Wittinghofer, A. (2007). Insight into catalysis of a unique GTPase reaction by a combined biochemical and FTIR approach. Journal of Molecular Biology 367, 983.CrossRefGoogle ScholarPubMed
Chen, W., Wilborn, M. & Rudolph, J. (2000). Dual-specific Cdc25B phosphatase: in search of the catalytic acid. Biochemistry 39, 10781–10789.CrossRefGoogle ScholarPubMed
Cheng, H., Sukal, S., Callender, R. & Leyh, T. S. (2001). γ-phosphate protonation and pH-dependent infolding of the Ras·GTP·Mg2+ complex A vibrational spectroscopy study. Journal of Molecular Biology 276, 9931–9935.Google Scholar
Cherepanov, D. A., Mulkidjanian, A. Y. & Junge, W. (1999). Transient accumulation of elastic energy in proton translocating ATP synthase. FEBS Letters 449, 1–6.CrossRefGoogle ScholarPubMed
Chin, J., Banaszcyk, M., Jubian, V. & Zou, X. (1989a). Cobalt(III) complex-promoted hydrolysis of phosphate diesters: comparison in reactivity of rigid cis-diaquo(tetraaza)cobalt(III) complexes. Journal of the American Chemical Society 111, 186–190.CrossRefGoogle Scholar
Chin, J., Banaszczyk, M., Jubian, V. & Zou, X. (1989b). Cobalt(III) complex-promoted hydrolysis of phosphate diesters: comparison in reactivity of rigid cis-diaquo(tetraaza)cobalt(III) complexes. Journal of the American Chemical Society 111, 186–190.CrossRefGoogle Scholar
Chung, H.-H., Benson, D. R., Cornish, V. W. & Schultz, P. G. (1993a). Probing the role of loop 2 in Ras function with unnatural amino acids. Proceedings of the National Academy of Sciences of the United States of America 90, 10145–10149.CrossRefGoogle ScholarPubMed
Chung, H.-H., Benson, D. R. & Schultz, P. G. (1993b). Probing the structure and mechanism of Ras protein with an expanded genetic code. Science 259, 806–809.CrossRefGoogle ScholarPubMed
Cleland, W. W. & Hengge, A. C. (2006). Enzymatic mechanisms of phosphate and sulfate transfer. Chemical Reviews 106, 3252–3278.CrossRefGoogle ScholarPubMed
Cohen, P. (2002). Protein kinases – the major drug targets of the twenty-first century? Nature Reviews. Drug Discovery 1, 309–315.CrossRefGoogle ScholarPubMed
Cohen, S., Carpenter, G. & King, L. J. (1980). Epidermal growth factor-receptor-protein kinase interactions. Co-purification of receptor and epidermal growth factor-enhanced phopshorylation activity. The Journal of Biological Chemistry 255, 4834–4842.CrossRefGoogle Scholar
Coleman, D. E. & Sprang, S. R. (1999). Reaction dynamics of G-protein catalyzed hydrolysis of GTP as viewed by X-ray crystallographic snapshots of Giα1. Methods in Enzymology 308, 70–92.CrossRefGoogle Scholar
Cool, R. H. & Parmeggiani, A. (1991). Substitution of histidine-84 and the GTPase mechanism of elongation factor-Tu. Biochemistry 30, 362–366.CrossRefGoogle ScholarPubMed
Cottrel, T. L. (1958). The Strengths of Chemical Bonds, 2nd edn. London: Butterworths.Google Scholar
Czub, J. & Grubmueller, H. (2011). Torsional elasticity and energetics of F1-ATPase. Proceedings of the National Academy of Sciences of the United States of America 108, 7408–7413.CrossRefGoogle ScholarPubMed
Dall'acqua, W. & Carter, P. (2000). Substrate-assisted catalysis: molecular basis and biological significance. Protein Science: A Publication of the Protein Society 9, 1–9.CrossRefGoogle ScholarPubMed
Davis, A. M., Hall, A. D. & Williams, A. (1988). Charge description of base-catalyzed alcoholysis of Aryl phosphodiesters – a ribonuclease model. Journal of the American Chemical Society 110, 5105–5108.CrossRefGoogle Scholar
Daviter, T., Wieden, H. J. & Rodnina, M. V. (2003). Essential role of histidine 84 in elongation factor Tu for the chemical step of GTP hydrolysis on the ribosome. Journal of Molecular Biology 332, 689–699.CrossRefGoogle ScholarPubMed
De Grauuw, M., Hensbergen, P. & Van Der Water, B. (2006). Phospho-proteomic analysis of cellular signaling. Electrophoresis 27, 2676–2686.CrossRefGoogle Scholar
De Vivo, M., Cavalli, A., Carloni, P. & Recanatini, M. (2007). Computationl study of the phosphoryl transfer catalyzed by a cyclin-dependent kinase. Chemistry 13, 8437–8444.CrossRefGoogle Scholar
Dejaegere, A. & Karplus, M. (1993). Hydrolysis rate difference between cyclic and acyclic phosphate esters: solvation versus strain. Journal of the American Chemical Society 115, 5316–5317.CrossRefGoogle Scholar
Dejaegere, A., Liang, X. & Karplus, M. (1994). Phosphate ester hydrolysis: calculation of gas-phase reaction paths and solvation effects. Journal of the Chemical Society Faraday Transactions 90, 1763–1770.CrossRefGoogle Scholar
Di Sabato, G. & Jencks, W. P. (1961). Mechanism and catalysis of reactions of acyl phosphates. II. Hydrolysis. Journal of the American Chemical Society 83, 4400–4405.CrossRefGoogle Scholar
Dittrich, M., Hayashi, S. & Schulten, K. (2003). On the mechanism of ATP hydrolysis in F1-ATPase. Biophysical Journal 85, 2253–2266.CrossRefGoogle ScholarPubMed
Downward, J., Parker, P. & Waterfield, M. D. (1984). Autophosphorylation sites on the epidermal growth factor receptor. Nature 311, 483–485.CrossRefGoogle ScholarPubMed
Drake, J. M., Graham, N. A., Stoyanova, T., Sedghi, A., Goldstein, A. S., Cai, H., Smith, D. A., Zhang, H., Komisopoulou, E., Huang, J., Graeber, T. G. & Witte, O. N. (2012). Oncogene-specific activation of tyrosine kinase networks during prostate cancer progression. Proceedings of the National Academy of Sciences of the United States of America 109, 1643–1648.CrossRefGoogle ScholarPubMed
Du, X. L., Black, G. E., Lecchi, P., Abramson, F. P. & Sprang, S. R. (2004). Kinetic isotope effects in Ras-catalyzed GTP hydrolysis: evidence for a loose transition state. Proceedings of the National Academy of Sciences of the United States of America 101, 8858–8863.CrossRefGoogle ScholarPubMed
Du, X. L., Frei, H. & Kim, S. H. (2000). The mechanism of GTP hydrolysis by Ras probed by Fourier transform infrared spectroscopy. The Journal of Biological Chemistry 275, 8492–8500.CrossRefGoogle ScholarPubMed
Dukanovic, J. & Rapaport, D. (2011). Multiple pathways in the integration of proteins into the mitochondrial outer membrane. Biochimica et Biophysica Acta – Biomembranes 1808, 971–980.CrossRefGoogle ScholarPubMed
Echols, H. & Goodman, M. F. (1991). Fidelity mechanisms in DNA replication. Annual Review of Biochemistry 60, 477–511.CrossRefGoogle ScholarPubMed
Edwards, D. R., Lohman, D. C. & Wolfenden, R. (2012). Catalytic proficiency: the extreme case of S–O cleaving sulfatases. Journal of the American Chemical Society 134, 525–531.CrossRefGoogle ScholarPubMed
Ehrenberg, M. (2009). Nobel prize in chemistry 2009 – scientific background, http://nobelprize.Org/nobel_prizes/chemistry/laureates/2009/sci.htmlGoogle Scholar
Emsley, J. (2000). The shocking history of phosphorus: a biography of the devil's element, pp. 133–158. London, England: Macmillan publishers Ltd.Google Scholar
Evans, B., Tishmack, P. A., Pokalsky, C., Zhang, M. & Van Etten, R. L. (1996). Site-directed mutagenesis, kinetic and spectroscopic studies of the P-loop residues in a low molecular weight protein tyrosine phosphatase. Biochemistry 35, 13609–13617.CrossRefGoogle Scholar
Fanning, E. (1992). Simian virus 40 large T antigen: the puzzle, the pieces, and the emerging picture. Journal of Virology 66, 1289–1293.CrossRefGoogle ScholarPubMed
Fardilha, M., Esteves, S. L., Korrodi-Gregório, L., Da Cruz E Silva, O. A. & Da Cruz E Silva, F. F. (2010). The physiological relevance of protein phosphatase 1 and its interacting proteins to health and disease. Current Medicinal Chemistry 17, 3996–4017.CrossRefGoogle ScholarPubMed
Feig, M., Zacharias, M. & Pettitt, B. M. (2001). Conformations of an adenine bulge in a DNA octamer and its influence on DNA structure from molecular dynamics simulations. Biophysical Journal 81, 352–370.CrossRefGoogle Scholar
Fekry, M. I., Tipton, P. A. & Gates, K. S. (2011). Kinetic consequences of replacing the internucleotide phosphorus atoms in DNA with arsenic. ACS Chemistry & Biology 6, 127–130.CrossRefGoogle ScholarPubMed
Feng, G., Tanifum, E. A., Adams, H., Hengge, A. C. & Williams, N. H. (2009). Mechanism and transition state structure of aryl methylphosphonate esters doubly coordinated to a dinuclear cobalt(III) center. Journal of the American Chemical Society 131, 12771–12779.CrossRefGoogle ScholarPubMed
Fersht, A. (1999). Structure and Mechanism in Protein Science. A Guide to Enzyme Catalysis and Protein Folding. New York: W. H. Freeman and Company.Google Scholar
Flaks, J. G., Erwin, M. J. & Buchanan, J. M. (1957). Biosynthesis of the purines: XVI. The synthesis of adenosine 5′-phosphate and 5-amino-4 imidazolecarboxamide ribotide by a nucleotide pyrophosphorylase. The Journal of Biological Chemistry 228, 201–213.CrossRefGoogle Scholar
Flichtinski, D., Sharabi, O., Ruppel, A., Vetter, I. R., Herrmann, C. & Shifman, J. M. (2010). What makes Ras an efficient molecular switch: a computational, biophysical and structural study of Ras-GRP interactions with mutants of Raf. Journal of Molecular Biology 399, 422–435.CrossRefGoogle Scholar
Florián, J., Åqvist, J. & Warshel, A. (1998). On the reactivity of phosphate monoester dianions in aqueous solution: Brønsted linear free-energy relationships do not have an unique mechanistic interpretation. Journal of the American Chemical Society 120, 11524–11525.CrossRefGoogle Scholar
Florián, J., Goodman, M. F. & Warshel, A. (2002). Theoretical investigation of the binding free energies and key substrate-recognition components of the replication fidelity of human DNA polymerase β. Journal of Physical Chemistry B 106, 5739–5753.CrossRefGoogle Scholar
Florián, J., Goodman, M. F. & Warshel, A. (2003a). Computer simulation of the chemical catalysis of DNA polymerases: discriminating between alternative nucleotide insertion mechanisms for T7 DNA polymerase. Journal of the American Chemical Society 125, 8163–8177.CrossRefGoogle ScholarPubMed
Florián, J., Goodman, M. F. & Warshel, A. (2003b). Computer simulation studies of the fidelity of DNA polymerases. Biopolymers 68, 286–299.CrossRefGoogle ScholarPubMed
Florián, J., Goodman, M. F. & Warshel, A. (2005). Computer simulations of protein functions: searching for the molecular origin of the replication fidelity of DNA polymerases. Proceedings of the National Academy of Sciences of the United States of America 102, 6819–6824.CrossRefGoogle ScholarPubMed
Florián, J. & Warshel, A. (1997). A fundamental assumption about OH- attack in phosphate hydrolysis is not fully justified. Journal of the American Chemical Society 119, 5473–5474.CrossRefGoogle Scholar
Florián, J. & Warshel, A. (1998). Phosphate ester hydrolysis in aqueous solution: associative versus dissociative mechanisms. Journal of Physical Chemistry B 102, 719–734.CrossRefGoogle Scholar
Florián, J. & Warshel, A. (1999). Calculation of hydration entropies of hydrophobic, polar, and ionic solutes in the framework of the Langevin dipole solvation model. Journal of Physical Chemistry B 103, 10282–10288.CrossRefGoogle Scholar
Fothergill, M., Goodman, M. F., Petruska, J. & Warshel, A. (1995). Structure-energy analysis of the role of metal ions in phosphodiester bond hydrolysis by DNA polymerase I. Journal of the American Chemical Society 117, 11619–11627.CrossRefGoogle Scholar
Friedman, J. M., Freeman, S. & Knowles, J. R. (1988). The quest for free metaphosphate in solution: racemization at phosphorus in the transfer of the phospho group from aryl phosphate monoesters to tert-butyl alcohol in acetonitrile or in tert-butyl alcohol. Journal of the American Chemical Society 110, 1268–1275.CrossRefGoogle Scholar
Frushicheva, M. P., Cao, J. & Warshel, A. (2011). Challenges and advances in validating enzyme design proposals: the case of Kemp eliminase catalysis. Biochemistry 50, 3849–3858.CrossRefGoogle ScholarPubMed
Furuike, S., Hossain, M. D., Maki, Y., Adachi, K., Suzuki, T., Kohori, A., Itoh, H., Yoshida, M. & Kinosita, J. R. K. (2008). Axle-less F1-ATPase rotates in the correct direction. Science 319, 955–958.CrossRefGoogle ScholarPubMed
Futatsugi, N., Hata, M., Hoshino, T. & Tsuda, M. (1999). Ab initio study of the role of lysine 16 for the molecular switching mechanism of Ras protein p21. Biophysical Journal 77, 3287–3292.CrossRefGoogle ScholarPubMed
Galperin, M. Y., Bairoch, A. & Koonin, E. V. (1998). A superfamily of metalloenzymes unifies phosphopentomutase and cofactor-independent phosphoglycerate mutase with alkaline phosphatases and sulfatases. Protein Science: A Publication of the Protein Society 7, 1829–1835.CrossRefGoogle ScholarPubMed
Galperin, M. Y. & Jedrzejas, M. J. (2001). Conserved core structure and active site residues in alkaline phosphatase superfamily enzymes. Proteins: Structure Function and Bioinformatics 45, 318–324.CrossRefGoogle ScholarPubMed
Gani, D. & Wilkie, J. (1995). Stereochemical, mechanistic, and structural features of enzyme-catalysed phosphate monoester hydrolyses. Chemical Society Reviews 24, 55–63.CrossRefGoogle Scholar
Gao, Y. Q., Yang, W. & Karplus, M. (2005). A structure-based model for the synthesis and hydrolysis of ATP by F1-ATPase. Cell 123, 195–205.CrossRefGoogle ScholarPubMed
Gerlt, J. A. & Gassman, P. G. (1993). Understanding the rates of certain enzyme-catalyzed reactions: proton abstraction from carbon acids, Acyl-transfer reactions, and displacement reactions of phosphodiesters. Biochemistry 32, 11943.CrossRefGoogle ScholarPubMed
Geyer, M., Herrmann, C., Wohlgemuth, S., Wittinghofer, A. & Kalbitzer, H. R. (1997). Structure of the Ras-binding domain of RalGEF and implications for Ras binding and signalling. Nature Structural Biology 4, 694–699.CrossRefGoogle ScholarPubMed
Gideon, P., John, J., Frech, M., Lautwein, A., Clark, R., Scheffler, J. E. & Wittinghofer, A. (1992). Mutational and kinetic analyses of the GTPase-activating protein (GAP)-p21 interaction: the C-terminal domain of GAP is not sufficient for full activity. Molecular and Cellular Biology 12, 2050–2056.Google Scholar
Glaves, R., Mathias, G. & Marx, D. (2012). Mechanistic insights into the hydrolysis of a nucleoside triphosphate model in neutral and acidic solution. Journal of the American Chemical Society 134, 6995–7000.CrossRefGoogle ScholarPubMed
Glennon, T. M., Villà, J. & Warshel, A. (2000). How does GAP catalyze the GTPase reaction of Ras? A computer simulation study. Biochemistry 39, 9641–9651.CrossRefGoogle Scholar
Glennon, T. M. & Warshel, A. (1998). Energetics of the catalytic reaction of ribonuclease A: a computational study of alternative mechanisms. Journal of the American Chemical Society 120, 10234–10247.CrossRefGoogle Scholar
Glusker, J. R., Katz, A. K. & Bock, C. W. (1999). Metal ions in biological systems. Rigaku Journal 16, 8–16.Google Scholar
Golicnick, M., Olguin, L. F., Feng, G., Baxter, N. J., Waltho, J. P., Williams, N. H. & Hollfelder, F. (2009). Kinetic analysis of β-phosphoglucomutase and its inhibition by magnesium fluoride. Journal of the American Chemical Society 131, 1575–1588.CrossRefGoogle Scholar
Goodman, M. F. (2002). Error-prone repair DNA polymerases in prokaryotes and eukaryotes. Annual Review of Biochemistry 71, 17–50.CrossRefGoogle ScholarPubMed
Goodman, M. F., Creighton, S., Bloom, L. B. & Petruska, J. (1993). Biochemical basis of DNA replication fidelity. Critical Reviews in Biochemistry and Molecular Biology 28, 83–126.CrossRefGoogle ScholarPubMed
Graham, D. L., Lowe, P. N., Grime, G. W., Marsh, M., Rittinger, K., Smerdon, S. J., Gamblin, S. J. & Eccleston, J. F. (2002). MgF3− as a transition state analog of phopshoryl transfer. Chemistry & Biology 9, 375–381.CrossRefGoogle Scholar
Graziano, M. P. & Gilman, A. G. (1989). Synthesis in Escherichia coli of GTPase-deficiect mutants of Gsα. The Journal of Biological Chemistry 264, 15475–15482.CrossRefGoogle Scholar
Grigorenko, B. L., Nemukhin, A. V., Shadrina, M. S., Topol, I. A. & Burt, S. K. (2007a). Mechanisms of guanosine triphosphate hydrolysis by Ras and Ras-GAP proteins as rationalized by ab initio QM/MM simulations. Proteins: Structure Function and Bioinformatics 66, 456–466.CrossRefGoogle ScholarPubMed
Grigorenko, B. L., Nemukhin, A. V., Topol, I. A., Cachau, R. E. & Burt, S. K. (2005). QM/MM modeling the Ras-GAP catalyzed hydrolysis of guanosine triphosphate. Proteins: Structure Function and Bioinformatics 60, 495–503.CrossRefGoogle ScholarPubMed
Grigorenko, B. L., Rogov, A. V. & Nemukhin, A. V. (2006). Mechanism of triphosphate hydrolysis in aqueous solution: QM/MM simulations in water clusters. Journal of Physical Chemistry B 110, 4407–4412.CrossRefGoogle ScholarPubMed
Grigorenko, B. L., Rogov, A. V., Topol, I. A., Burt, S. K., Martinez, H. M. & Nemukhin, A. V. (2007b). Mechanism of the myosin catalyzed hydrolysis of ATP as rationalized by molecular modeling. Proceedings of the National Academy of Sciences of the United States of America 104, 7057–7061.CrossRefGoogle ScholarPubMed
Grigorenko, B. L., Shadrina, M. S., Topol, I. A., Collins, J. R. & Nemukhin, A. V. (2008). Mechanism of the chemical step for the guanosine triphosphate (GTP) hydrolysis catalyzed by elongation factor Tu. Biochimica et Biophysica Acta – Proteins and Proteomics 1784, 1908–1917.CrossRefGoogle ScholarPubMed
Grunwald, E. (1985). Reaction mechanism from structure-energy relations. 1. Base-catalyzed addition of alcohols to formaldehyde. Journal of the American Chemical Society 107, 4710–4715.CrossRefGoogle Scholar
Guan, K. L. & Dixon, J. E. (1991). Evidence for protein-tyrosine-phosphatase catalysis proceeding via a cysteine-phosphate intermediate. The Journal of Biological Chemistry 266, 17026–17030.CrossRefGoogle Scholar
Guerrier-Takeda, C., Gardiner, K., Marsh, T., Pace, N. & Altman, S. (1983). The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell 35, 849–857.CrossRefGoogle Scholar
Guthrie, J. P. (1977). Hydration and dehydration of phosphoric acid derivatives: free energies of formation of the pentacoordinate intermediates of phosphate ester hydrolysis and of monomeric metaphosphate. Journal of the American Chemical Society 99, 3991–4001.CrossRefGoogle Scholar
Guthrie, J. P. (1996). Multidimensional Marcus theory: an analysis of concerted reactions. Journal of the American Chemical Society 118, 12878–12885.CrossRefGoogle Scholar
Hale, S. P., Poole, L. B. & Gerlt, J. A. (1993). Mechanism of the reaction catalyzed by staphylococcal nuclease; identification of the rate-determining step. Biochemistry 32, 1479.CrossRefGoogle ScholarPubMed
Hall, C. R. & Inch, T. D. (1980). Phosphorus stereochemistry: mechanistic implications of the observed stereochemistry of bond forming and breaking processes at phosphorus in some 5- and 6-membered ring phosphorus esters. Tetrahedron 36, 2059–2095.CrossRefGoogle Scholar
Hammes, G. G., Benkovic, S. J. & Hammes-Schiffer, S. (2011). Flexibility, diversity, and cooperativity: pillars of enzyme catalysis. Biochemistry 50, 10422–10430.CrossRefGoogle ScholarPubMed
Hansson, T., Nordlund, P. & Åqvist, J. (1997). Energetics of nucleophile activation in a protein tyrosine phosphatase. Journal of Molecular Biology 265, 118–127.CrossRefGoogle Scholar
Hausner, T. P., Atmadja, J. & Nierhaus, K. H. (1987). Evidence that the G2661 region of 23S ribosomal-RNA is located at the ribosomal-binding sites of both elongation-factors. Biochimie 69, 911–923.CrossRefGoogle ScholarPubMed
Heesen, H. T., Gerwert, K. & Schlitter, J. (2007). Role of the arginine finger in Ras·RasGAP revealed by QM/MM calculations. FEBS Letters 581, 5677–5684.CrossRefGoogle Scholar
Henchman, M., Viggiano, A. A., Paulson, J. F., Freedman, A. & Wormhoudt, J. (1985). Thermodynamic and kinetic properties of the metaphosphate anion, PO3− in the gas phase. Journal of the American Chemical Society 107, 1453–1455.CrossRefGoogle Scholar
Hengge, A. C. (1999). Insights from Heavy-Atom Isotope Effects on Phosphoryl and Thiophosphoryl Transfer Reactions. Amsterdam: IOS Press.Google Scholar
Hengge, A. C. (2002). Isotope effects in the study of phosphoryl and sulfuryl transfer reactions. Accounts of Chemical Research 35, 105–112.CrossRefGoogle Scholar
Hengge, A. C. & Cleland, W. W. (1991). Phosphoryl-transfer reactions of phosphodiesters: characterization of transition states by heavy-atom isotope effects. Journal of the American Chemical Society 113, 5835–5841.CrossRefGoogle Scholar
Hengge, A. C., Edens, W. A. & Elsing, H. (1994). Transition-state structures for phosphoryl-transfer reactions of p-nitrophenyl phosphate. Journal of the American Chemical Society 116, 5045–5049.CrossRefGoogle Scholar
Hengge, A. C., Tobin, A. E. & Cleland, W. W. (1995). Studies of transition-state structures in phosphoryl transfer reactions of phosphodiesters of p-nitrophenol. Journal of the American Chemical Society 117, 5919–5926.CrossRefGoogle Scholar
Henzler-Wildman, K. A., Lei, M., Thai, V., Kerns, S. J., Karplus, M. & Kern, D. (2007a). A hierarchy of timescales in protein dynamics is linked to enzyme catalysis. Nature 450, 913–916.CrossRefGoogle ScholarPubMed
Henzler-Wildman, K. A., Thai, V., Lei, M., Ott, M., Wolf-Watz, M., Fenn, T., Pozharski, E., Wilson, M. A., Petsko, G. A., Karplus, M., Hubner, C. G. & Kern, D. (2007b). Intrinsic motions along an enzymatic reaction trajectory. Nature 450, 838–844.CrossRefGoogle ScholarPubMed
Herrmann, C., Martin, G. A. & Wittinghofer, A. (1995). Quantitative analysis of the complex between p21ras and the Ras-binding domain of the human Raf-1 protein kinase. The Journal of Biological Chemistry 270, 2901.CrossRefGoogle ScholarPubMed
Herschlag, D. & Jencks, W. P. (1987). The effect of divalent metal ions on the rate and transition-state structure of phosphoryl-transfer reactions. Journal of the American Chemical Society 109, 4665–4674.CrossRefGoogle Scholar
Herschlag, D. & Jencks, W. P. (1989a). Evidence that metaphosphate monoanion is not an intermediate in solvolysis reactions in aqueous solution. Journal of the American Chemical Society 111, 7579–7586.CrossRefGoogle Scholar
Herschlag, D. & Jencks, W. P. (1989b). Phosphoryl transfer to anionic oxygen nucleophiles. Nature of the transition state and electrostatic repulsion. Journal of the American Chemical Society 111, 7587–7596.CrossRefGoogle Scholar
Hoff, R. H. & Hengge, A. C. (1998a). Entropy and enthalpy contributions to solvent effects on phosphate monoester solvolosys. The importance of entropy effects in the dissociative transition state. The Journal of Organic Chemistry 63, 6680–6688.CrossRefGoogle Scholar
Hoff, R. H. & Hengge, A. C. (1998b). Entropy and enthalpy contributions to solvent effects on phosphate monoester solvolysis. The importance of entropy effects in the dissociative transition state. The Journal of Organic Chemistry 63, 6680–6688.CrossRefGoogle Scholar
Hoff, R. H., Larsen, P. & Hengge, A. C. (2001). Isotope effects and medium effects on sulfuryl transfer reactions. Journal of the American Chemical Society 123, 9338–9344.CrossRefGoogle ScholarPubMed
Hollfelder, F. & Herschlag, D. (1995a). The nature of the transition state for enzyme-catalyzed phopshoryl transfer. Hydrolysis of O-arylphosphorothioates by alkaline phosphatase. Biochemistry 34, 12255–12264.CrossRefGoogle Scholar
Hollfelder, F. & Herschlag, D. (1995b). The nature of the transition state for enzyme-catalyzed phosphoryl transfer. Hydrolysis of O-aryl phosphorothioates by alkaline phosphatase. Biochemistry 34, 12255.CrossRefGoogle ScholarPubMed
Holtz, K. M., Cartrine, I. E., Hengge, A. C. & Kantrowitz, E. (2000). General acid-base catalysis of complex reactions in water. Biochemistry 39, 9451–9458.CrossRefGoogle Scholar
Hoofs Van Huijsduijnen, R., Wälchi, S., Ibberson, M. & Harrenga, A. (2002). Protein tyrosine phosphatases as drug targets: PTP1B and beyond. Expert Opinion on Therapeutic Targets 6, 637–647.CrossRefGoogle Scholar
Hou, G. & Cui, Q. (2012). QM/MM analysis suggests that alkaline phosphatase (AP) and nucleotide pyrophosphatase/phosphodiesterase slightly tighten transition state for phosphate diester hydrolysis relative to solution: implication for catalytic promiscuity in the AP superfamily. Journal of the American Chemical Society 134, 229–246.CrossRefGoogle ScholarPubMed
Hu, C.-H. & Brinck, T. (1999). Theoretical studies of the hydrolysis of the methyl phosphate anion. Journal of Physical Chemistry A 103, 5379–5386.CrossRefGoogle Scholar
Hübscher, U., Maga, G. & Spadari, S. (2002). Eukaryotic DNA polymerases. Annual Review of Biochemistry 71, 133–163.CrossRefGoogle ScholarPubMed
Huheey, J. E., Keitler, E. A. & Keitler, R. L. (1993). Inorganic Chemistry, 4th edn. New York: Harper Collins.Google Scholar
Humphry, T., Forconi, M., Williams, N. H. & Hengge, A. C. (2004). Altered mechanisms of reactions of phosphate esters bridging a dinuclear metal center. Journal of the American Chemical Society 126, 11864–11869.CrossRefGoogle ScholarPubMed
Hunter, T. (1995). Protein kinases and phosphatases: the Yin and Yang of protein phosphorylation and signalling. Cell 80, 225–236.CrossRefGoogle Scholar
Hunter, T. (2000). Signaling–2000 and beyond. Cell 100, 113–127.CrossRefGoogle ScholarPubMed
Hunter, T. (2007). The age of crosstalk: phosphorylation, ubiquitination, and beyond. Molecular Cell 28, 730–738.CrossRefGoogle ScholarPubMed
Hunter, T. & Cooper, J. A. (1985). Protein-tyrosine kinases. Annual Review of Biochemistry 54, 897–930.CrossRefGoogle ScholarPubMed
Hwang, J.-K., King, G., Creighton, S. & Warshel, A. (1988). Simulation of free energy relationships and dynamics of SN2 reactions in aqueous solution. Journal of the American Chemical Society 110, 5297–5311.CrossRefGoogle Scholar
Hwang, J.-K. & Warshel, A. (1993). A quantized classical path approach for calculations of quantum mechanical rate constants. Journal of Physical Chemistry 97, 10053–10058.CrossRefGoogle Scholar
Hwang, J.-K. & Warshel, A. (1996). How important are quantum mechanical nuclear motions in enzyme catalysis? Journal of the American Chemical Society 118, 11745–11751.CrossRefGoogle Scholar
Iche-Tarrat, N., Barthelat, J. C., Rinaldi, D. & Vigroux, A. (2005). Theoretical studies of the hydroxide-catalyzed P–O cleavage reactions of neutral phosphate triesters and diesters in aqueous solution: examination of the changes induced by H/Me substitution. Journal of Physical Chemistry B 109, 22570–22580.CrossRefGoogle ScholarPubMed
Iché-Tarrat, N., Ruiz-Lopez, M., Barthelat, J.-C. & Vigroux, A. (2007). Theoretical evaluation of the substrate-assisted catalysis mechanism for the hydrolysis of phosphate monoester dianions. Chemistry–A European Journal 13, 3617–3629.CrossRefGoogle ScholarPubMed
Inbal, B., Shani, G., Cohen, O., Kissil, J. & Kimchi, A. (2000). Death-associated protein kinase-related protein 1, a novel serine/threonine kinase involved in apoptosis. Molecular and Cellular Biology 20, 1044–1054.CrossRefGoogle ScholarPubMed
Jacquet, E. & Parmeggiani, A. (1988). Structure-function relationships in the GTP binding domain of EF-Tu – mutation of Val20, the residue homologous to position 12 in p21. The EMBO Journal 7, 2861–2867.CrossRefGoogle ScholarPubMed
Jankowski, S., Quin, L. D., Paneth, P. & O'Leary, M. H. (1994). Kinetic isotope effects on ethyl metaphosphate transfer from a phosphoramidate to ethanol. Journal of the American Chemical Society 116, 11675–11677.CrossRefGoogle Scholar
Jencks, W. P. (1969). Catalysis in Chemistry and Enzymology. New York: McGraw-Hill.Google Scholar
Jencks, W. P. (1972). General acid-base catalysis of complex reactions in water. Chemical Reviews 72, 705–718.CrossRefGoogle Scholar
Jencks, W. P. (1980). When is an intermediate not an intermediate? Enforced mechanisms of general acid-base, catalyzed, carbocation, carbanion, and ligand exchange reaction. Accounts of Chemical Research 13, 161–169.CrossRefGoogle Scholar
Jencks, W. P. (1985). A primer for the bema hapothle. An empirical approach to the characterization of changing transition-state structures. Chemical Reviews 85, 511–527.CrossRefGoogle Scholar
Jencks, W. P. (1987). Catalysis in Chemistry and Enzymology. New York: Dover.Google Scholar
Jensen, R. A. (1976). Enzyme recruitment in evolution of new function. Annual Reviews of Microbiology 30, 409–425.CrossRefGoogle ScholarPubMed
Johnson, K. A. (1993). Conformational coupling in DNA polymerase fidelity. Annual Review of Biochemistry 62, 685–713.CrossRefGoogle ScholarPubMed
Johnson, K. A. (2008). Role of induced fit in enzyme specificity: a molecular forward/reverse switch. The Journal of Biological Chemistry 283, 26297–26301.CrossRefGoogle ScholarPubMed
Johnson, T. O., Ermolieff, J. & Jirousek, M. R. (2002). Protein tyrosine phosphatase 1B inhibitors for diabetes. Nature Reviews. Drug Discovery 1, 696–708.CrossRefGoogle ScholarPubMed
Jonas, S. & Hollfelder, F. (2009). Mapping catalytic promiscuity in the alkaline phosphatase superfamily. Pure and Applied Chemistry 81, 731–742.CrossRefGoogle Scholar
Jonas, S., Van Loo, B., Hyvönen, M. & Hollfelder, F. (2008). A new member of the alkaline phosphatase superfamily with a formylglycine nucleophile: structural and kinetic characterisation of a phosphate monoester hydrolyase/phosphodiesterase from Rhizobium leguminosarum. Journal of Molecular Biology 384, 120–136.CrossRefGoogle Scholar
Joyce, C. M. & Benkovic, S. J. (2004). DNA polymerase fidelity: kinetics, structure, and checkpoints. Biochemistry 43, 14317–14324.CrossRefGoogle ScholarPubMed
Kamerlin, S. C. L. (2011a). Theoretical comparison of p-nitrophenyl phosphate and sulfate hydrolysis in aqueous solution: implications for enzyme catalyzed sulfuryl transfer. The Journal of Organic Chemistry 76, 9228–9238.CrossRefGoogle ScholarPubMed
Kamerlin, S. C. L., Florián, J. & Warshel, A. (2008a). Associative versus dissociative mechanisms of phosphate monoester hydrolysis: on the interpretation of activation entropies. Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry 9, 1767–1773.CrossRefGoogle ScholarPubMed
Kamerlin, S. C. L., Haranczyk, M. & Warshel, A. (2009a). Are mixed explicit/implicit solvation models reliable for studying phosphate hydrolysis? A comparative study of continuum, explicit and mixed solvation models. Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry 10, 1125–1134.CrossRefGoogle ScholarPubMed
Kamerlin, S. C. L., Haranczyk, M. & Warshel, A. (2009b). Progress in ab initio QM/MM free-energy simulations of electrostatic energies in proteins: accelerated QM/MM studies of pKa, redox reactions, and solvation free energies. Journal of Physical Chemistry B 113, 1253–1272.CrossRefGoogle ScholarPubMed
Kamerlin, S. C. L., Mckenna, C. E., Goodman, M. F. & Warshel, A. (2009c). A computational study of the hydrolysis of dGTP analogues with halomethylene-modified leaving groups in solution: implications for the mechanism of DNA polymerases. Biochemistry 48, 5963–5971.CrossRefGoogle ScholarPubMed
Kamerlin, S. C. L., Rucker, R. & Boresch, S. (2007). A molecular dynamics study of WPD-loop flexibility in PTP1B. Biochemical and Biophysical Research Communications 356, 1011–1016.CrossRefGoogle ScholarPubMed
Kamerlin, S. C. L., Sharma, P. K., Chu, Z. T. & Warshel, A. (2010). Ketosteroid isomerase provides further support for the idea that enzymes work by electrostatic preorganization. Proceedings of the National Academy of Sciences of the United States of America 107, 4075–4080.CrossRefGoogle ScholarPubMed
Kamerlin, S. C. L., Vicatos, S. & Warshel, A. (2011). Coarse-grained (multiscale) simulations in studies of biophysical and chemical systems. Annual Review of Physical Chemistry 62, 41–64.CrossRefGoogle ScholarPubMed
Kamerlin, S. C. L. & Warshel, A. (2009). On the energetics of ATP hydrolysis in solution. Journal of Physical Chemistry B 113, 15692–15698.CrossRefGoogle ScholarPubMed
Kamerlin, S. C. L. & Warshel, A. (2010). At the dawn of the 21st century: is dynamics the missing link for understanding enzyme catalysis? Proteins: Structure Function and Bioinformatics 78, 1339–1375.CrossRefGoogle ScholarPubMed
Kamerlin, S. C. L. & Warshel, A. (2011a). The empirical valence bond model: theory and applications. Computational Molecular Science 1, 30–45.CrossRefGoogle Scholar
Kamerlin, S. C. L. & Warshel, A. (2011b). Multiscale modeling of biological problems. Physical Chemistry Chemical Physics 13, 10401–10411.CrossRefGoogle Scholar
Kamerlin, S. C. L. & Wilkie, J. (2007). The role of metal ions in phosphate ester hydrolysis. Organic & Biomolecular Chemistry 5, 2098–2108.CrossRefGoogle ScholarPubMed
Kamerlin, S. C. L. & Wilkie, J. (2011). The effect of leaving group on mechanistic preference in phosphate monoester hydrolysis. Organic & Biomolecular Chemistry 9, 5394–5406.CrossRefGoogle Scholar
Kamerlin, S. C. L., Williams, N. H. & Warshel, A. (2008b). Dineopentyl phosphate hydrolysis: evidence for stepwise water attack. The Journal of Organic Chemistry 73, 6960–6969.CrossRefGoogle ScholarPubMed
Khan, S. A. & Kirby, A. J. (1970). The reactivity of phosphate esters. Multiple structure–reactivity correlations for the reactions of triesters with nucleophiles. Journal of the Chemical Society B 1172–1182.CrossRefGoogle Scholar
Khersonsky, O., Roodveldt, C. & Tawfik, D. S. (2006). Enzyme promiscuity: evolutionary and mechanistic aspects. Current Opinion in Chemistry & Biology 10, 498–508.CrossRefGoogle ScholarPubMed
Khersonsky, O. & Tawfik, D. S. (2010). Enzyme promiscuity: a mechanistic and evolutionary perspective. Annual Review of Biochemistry 79, 471–505.Google ScholarPubMed
Kim, E. E. & Wyckoff, H. W. (1991). Reaction mechanism of alkaline phosphatase based on crystal structures: two metal ion catalysis. Journal of Molecular Biology 218, 449–464.CrossRefGoogle ScholarPubMed
Kim, S. J., Beard, W. A., Harvey, J., Shock, D. D., Knutson, J. R. & Wilson, S. H. (2003). Rapid segmental and subdomain motions of DNA polymerase β. The Journal of Biological Chemistry 278, 5072–5081.CrossRefGoogle ScholarPubMed
Kirby, A. J. & Jencks, W. P. (1965a). The reactivity of nucleophilic reagents toward the p-nirophenyl phosphate dianions. Journal of the American Chemical Society 87, 3209–3216.CrossRefGoogle Scholar
Kirby, A. J. & Varvoglis, A. G. (1967a). The reactivity of phosphate esters. Monoester hydrolysis. Journal of the American Chemical Society 89, 415–423.CrossRefGoogle Scholar
Kirby, A. J. & Varvoglis, A. G. (1968a). The reactivity of phosphate esters: reactions of monoesters with nucleophiles. Nucleophilicity independent of basicity in a bimolecular substitution reaction. Journal of the American Chemical Society B 135–141.CrossRefGoogle Scholar
Kirby, A. J. & Varvoglis, A. G. (1968b). The reactivity of phosphate esters: reactions of monoesters with nucleophiles. Nucleophilicity independent of basicity in a bimolecular substitution reaction. Journal of the American Chemical Society B 135–141.CrossRefGoogle Scholar
Kirby, A. J. & Younas, M. (1970a). The reactivity of phosphate esters. Reactions of diesters with nucleophiles. Journal of the American Chemical Society B 510–513.CrossRefGoogle Scholar
Kirby, A. J. & Younas, M. (1970b). The reactivity of phosphate esters. Reactions of diesters with nucleophiles. Journal of the American Chemical Society B 1165–1172.CrossRefGoogle Scholar
Kirby, J. A. & Jencks, W. P. (1965b). The reactivity of nucleophillic reagents towards the p-nitrophenyl phosphate dianion. Journal of the American Chemical Society 87, 3209–3216.CrossRefGoogle Scholar
Kirby, J. A. & Varvoglis, A. G. (1967b). The reactivity of phosphate monoester hydrolysis. Journal of the American Chemical Society 89, 415–423.CrossRefGoogle Scholar
Kirby, J. A. & Younas, M. (1970c). The reactivity of phosphate esters. Diester hydrolysis. Journal of the American Chemical Society B 510–513.CrossRefGoogle Scholar
Kirby, T. W., Derose, E. F., Beard, W. A., Wilson, S. H. & London, R. E. (2005). A thymine isostere in the templating position disrupts assembly of the closed DNA polymerase β ternary complex. Biochemistry 44, 15230–15237.CrossRefGoogle ScholarPubMed
Kirmizialtin, S., Nguyen, V., Johnson, K. A. & Elber, R. (2012). How conformational dynamics of DNA polymerase select correct substrates: experiments and simulations. Structure 20, 618–627.CrossRefGoogle ScholarPubMed
Klähn, M., Rosta, E. & Warshel, A. (2006). On the mechanism of hydrolysis of phosphate monoesters dianions in solutions and proteins. Journal of the American Chemical Society 128, 15310–15323.CrossRefGoogle ScholarPubMed
Knight, W. B., Weiss, P. M. & Cleland, W. W. (1986). Determination of equilibrium 18O isotope effects on the deprotonation of phosphate and phosphate esters and the anomeric effect on deprotonation of glucose 6-phosphate. Journal of the American Chemical Society 108, 2579–2761.CrossRefGoogle Scholar
Knudsen, C., Wieden, H. J. & Rodnina, M. V. (2001). The importance of structural transitions of the switch ii region for the functions of elongation factor Tu on the ribosome. The Journal of Biological Chemistry 276, 22183–22190.CrossRefGoogle ScholarPubMed
Koga, N. & Takada, S. (2006). Folding-based molecular simulations reveal mechanisms of the rotary motor F1-ATPase. Proceedings of the National Academy of Sciences of the United States of America 103, 5367–5372.CrossRefGoogle ScholarPubMed
Kolmodin, K. & Åqvist, J. (1999). Computational modeling of the rate limiting step in low molecular weight protein tyrosine phosphatase. FEBS Letters 456, 301–305.CrossRefGoogle ScholarPubMed
Kolmodin, K. & Åqvist, J. (2001). The catalytic mechanism of protein tyrosine phosphatases revisited. FEBS Letters 498, 208–213.CrossRefGoogle ScholarPubMed
Kolmodin, K., Nordlund, P. & Aqvist, J. (1999). Mechanism of substrate dephosphorylation in low M-r protein tyrosine phosphatase. Proteins 36, 370–379.3.0.CO;2-9>CrossRefGoogle Scholar
Kornberg, A. & Baker, T. A. (1992). DNA Replication. New York: W. H. Freeman.Google Scholar
Kornberg, A., Lieberman, I. & Simms, E. S. (1955). Enzymatic synthesis and properties of 5-phosphoribosylpyrophosphatase. The Journal of Biological Chemistry 215, 389–402.CrossRefGoogle Scholar
Koshland, D. E. (1995). The key-lock theory and the induced fit theory. Angewandte Chemie (International ed. in English) 33, 2375–2378.CrossRefGoogle Scholar
Kosloff, M., Zor, T. & Selinger, Z. (2000). Substrate-assisted catalysis: implications for biotechnology and drug design. Drug Development & Research 50, 250–257.3.0.CO;2-0>CrossRefGoogle Scholar
Krab, I. M. & Parmeggiani, A. (1999). Mutagenesis of three residues, isoleucine-60, threonine-61, and aspartic acid-80, implicated in the GTPase activity of Escherichia coli elongation factor Tu. Biochemistry 38, 13035–13041.CrossRefGoogle ScholarPubMed
Kraut, D. A., Sigala, P. A., Pybus, B., Liu, C. W., Ringe, D., Petsko, G. A. & Herschlag, D. (2006). Testing electrostatic complementarity in enzyme catalysis: hydrogen bonding in the ketosteroid isomerase oxyanion hole. PLoS Biology 4, 0501–0519.CrossRefGoogle ScholarPubMed
Krengel, U., Schlichting, L., Scherer, A., Schumann, R., Frech, M., John, J., Kabsch, W., Pai, E. F. & Wittinghofer, A. (1990). Three-dimensional structures of H-Ras P21 mutants – molecular basis for their inability to function as signal transduction switch molecules. Cell 62, 539–548.CrossRefGoogle Scholar
Kruger, K., Grabowski, P. J., Zaug, A. J., Sands, J., Gottschling, D. E. & Cech, T. R. (1982). Self-splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of tetrahymena. Cell 31, 147–157.CrossRefGoogle ScholarPubMed
Kumamoto, J., Cox, J. R. JR., & Westheimer, F. H. (1956). Barium ethylene phosphate. Journal of the American Chemical Society 78, 4858–4860.CrossRefGoogle Scholar
Kunkel, T. A. & Bebenek, K. (2000). DNA replication fidelity. Annual Review of Biochemistry 69, 497–529.CrossRefGoogle ScholarPubMed
Kurz, J. L. (1978). The relationship of barrier shape to ‘linear’ free energy slopes and curvatures. Chemical Physics Letters 57, 243–246.CrossRefGoogle Scholar
Lad, C., Williams, N. H. & Wolfenden, R. (2003a). The rate of hydrolysis of phosphomonoester dianions and the exceptional catalytic proficiencies of protein and inositol phosphatases. Proceedings of the National Academy of Sciences of the United States of America 100, 5607–5610.CrossRefGoogle ScholarPubMed
Lad, C., Williams, N. H. & Wolfenden, R. (2003b). The rate of hydrolysis of phosphomonoester dianions and the exceptional catalytic proficiencies of protein and inositol phosphatases. Proceedings of the National Academy of Sciences of the United States of America 100, 5607–5610.CrossRefGoogle ScholarPubMed
Lahiri, S. D., Zhang, G. F., Dunaway-Mariano, D. & Allen, K. N. (2003). The pentacovalent phosphorus intermediate of a phosphoryl transfer reaction. Science 299, 2067–2071.CrossRefGoogle ScholarPubMed
Lambright, D. G., Noel, J. P., Hamm, H. E. & Sigler, P. B. (1994). Structural determinants for activation of the α-subunit of a heterotrimeric G protein. Nature 369, 621–628.CrossRefGoogle ScholarPubMed
Lancaster, L., Lambert, N. J., Maklan, E. J., Horan, L. H. & Noller, H. F. (2008). The sarcin–ricin loop of 23S rRNA is essential for assembly of the functional core of the 50S ribosomal subunit. RNA – A Publication of the RNA Society 14, 1999–2012.CrossRefGoogle ScholarPubMed
Lang, T. M., Maitra, M., Starcevic, D., Li, S. X. & Sweasy, J. (2004). A DNA polymerase β mutant from colon cancer cells induces mutations. Proceedings of the National Academy of Sciences of the United States of America 101, 6074–6079.CrossRefGoogle ScholarPubMed
Langen, R., Schweins, T. & Warshel, A. (1992). On the mechanism of guanosine triphosphate hydrolysis in ras p21 proteins. Biochemistry 31, 8691–8696.CrossRefGoogle ScholarPubMed
Larsen, A. K., Ouaret, D., El Ouadrani, K. & Petitprez, A. (2011). Targeting EGFR and VEGF(R) pathway cross-talk in tumor survival and angiogenesis. Pharmacology & Therapeutics 131, 80–90.CrossRefGoogle ScholarPubMed
Lassila, J. K. & Herschlag, D. (2008). Promiscuous sulfatase activity and thio-effects in a phosphodiesterase of the alkaline phosphatase superfamily. Biochemsitry 47, 12853–12859.CrossRefGoogle Scholar
Lassila, J. K., Zalatan, J. G. & Herschlag, D. (2011). Biological phosphoryl-transfer reactions: understanding mechanism and catalysis. Annual Review of Biochemistry 80, 669–702.CrossRefGoogle ScholarPubMed
Leclerc, F. & Karplus, M. (2006). Two-metal-ion mechanism for hammerhead-ribozyme catalysis. Journal of Physical Chemistry B 110, 3395–3409.CrossRefGoogle ScholarPubMed
Lee, F. S., Chu, Z. T., Bolger, M. B. & Warshel, A. (1992). Calculations of antibody antigen interactions – microscopic and semimicroscopic evaluation of the free-energies of binding of phosphorylcholine analogs to McPC603. Protein Engineering 5, 215–228.CrossRefGoogle ScholarPubMed
Lee, F. S., Chu, Z. T. & Warshel, A. (1993). Microscopic and semimicroscopic calculations of electrostatic energies in proteins by the POLARIS and ENZYMIX programs. Journal of Computational Chemistry 14, 161–185.CrossRefGoogle Scholar
Leffler, J. E., & Grunwald, E. (1963). Rates and Equilibria of Organic Reactions. New York: Wiley and Sons.Google Scholar
Li, G. & Zhang, X. C. (2004). GTP Hydrolysis Mechanism of Ras-like GTPases. Journal of Molecular Biology 340, 921.CrossRefGoogle ScholarPubMed
Li, G. H. & Cui, Q. (2004). Mechanochemical coupling in myosin: a theoretical analysis with molecular dynamics and combined QM/MM reaction path calculations. Journal of Physical Chemistry B 108, 3342–3357.CrossRefGoogle Scholar
Liao, X., Anjaneyulu, P. S. R., Curley, J. F., Hsu, M., Boehringer, M., Caruthers, M. H. & Piccirilli, J. A. (2001a). The tetrahymena ribozyme cleaves a 5′-methylene phosphonate monoester ∼102-fold faster than a normal phosphate diester: implications for enzyme catalysis of phosphoryl transfer reactions. Biochemistry 40, 10911–10926.CrossRefGoogle Scholar
Liao, X., Anjaneyulu, P. S. R., Curley, J. F., Hsu, M., Boehringer, M., Caruthers, M. H. & Piccirilli, J. A. (2001b). The tetrahymena ribozyme cleaves a 5′-ethylene phosphonate monoester 102-fold faster than a normal phosphate diester: implications for enzyme catalysis of phosphoryl transfer reactions. Biochemistry 40, 10911–10926.CrossRefGoogle Scholar
Liljas, A. (2004). Structural Aspects of Protein Synthesis. Singapore: World Scientific Publishing Co.CrossRefGoogle Scholar
Liljas, A., Ehrenberg, M. & Åqvist, J. (2011). Comment on ‘the mechanism for activation of GTP hydrolysis on the ribosome’. Science 333, 37.CrossRefGoogle ScholarPubMed
Lima, F. S., Chaimovich, H. & Cuccovia, I. M. (2012). Kinetics and product distribution of p-nitrophenyl phosphate dianion solvolysis in ternary DMSO/alcohol/water mixtures are compatible with metaphosphate formation. Journal of Physical Organic Chemistry 25, 9–13.CrossRefGoogle Scholar
Lin, P., Batra, V. K., Pedersen, L. C., Beard, W. A., Wilson, S. H. & Pedersen, L. G. (2008). Incorrect nucleotide insertion at the active site of a G: a mismatch catalyzed by DNA polymerase β. Proceedings of the National Academy of Sciences of the United States of America 105, 5670–5674.CrossRefGoogle Scholar
Lin, P., Pedersen, L. C., Batra, V. K., Beard, W. A., Wilson, S. H. & Pedersen, L. G. (2006). Energy analysis of chemistry for correct insertion by DNA polymerase β. Proceedings of the National Academy of Sciences of the United States of America 103, 13294–13299.CrossRefGoogle ScholarPubMed
Liu, H., Shi, Y., Chen, X. S. & Warshel, A. (2009). Simulating the electrostatic guidance of the vectorial translocations in hexameric helicases and translocases. Proceedings of the National Academy of Sciences of the United States of America 106, 7449–7454.CrossRefGoogle ScholarPubMed
Liu, H. & Warshel, A. (2007). The catalytic effect of dihydrofolate reductase and its mutants is determined by reorganization energies. Biochemistry 46, 6011–6025.CrossRefGoogle ScholarPubMed
Liu, Y., Gregersen, B. A., Lopez, X. & York, D. M. (2006). Density functional study of the in-line mechanism of methanolysis of cyclic phosphate and thiophosphate esters in solution: insights into thio effects in RNA transesterification. Journal of Physical Chemistry B 109, 19987–20003.CrossRefGoogle Scholar
Lonsdale, R., Hoyle, S., Grey, T., Ridder, L. & Mulholland, A. J. (2012). Determinants of reactivity and selectivity in soluble epoxide hydrolase from quantum mechanics/molecular mechanics modeling. Biochemistry 51, 1774–1786.CrossRefGoogle ScholarPubMed
López-Canut, V., Roca, M., Bertrán, J., Moliner, V. & Tuno, I. (2010). Theoretical study of phosphodiester hydrolysis in nucleotide pyrophosphatase/phosphodiesterase. Environmental effects on the reaction mechanism. Journal of the American Chemical Society 132, 6955–6963.CrossRefGoogle ScholarPubMed
Lopéz-Canut, V., Roca, M., Bertrán, J., Moliner, V. & Tuñon, I. (2011). Promiscuity in alkaline phosphatase superfamily. Unraveling evolution through molecular simulations. Journal of the American Chemical Society 133, 12050–12062.CrossRefGoogle ScholarPubMed
Lopez, X., Dejaegere, A., Leclerc, F., York, D. M. & Karplus, M. (2006). Nucleophilic attack on phosphate diesters: a density functional study of in-line reactivity in dianionic, monoanionic, and neutral systems. Journal of Physical Chemistry B 110, 11525–11539.CrossRefGoogle ScholarPubMed
Lopez, X. & York, D. M. (2003). Parameterization of semiempirical methods to treat nucleophilic attack to biological phosphates: AM1/d parameters for phosphorus. Theoretical Chemistry Accounts 109, 149–159.CrossRefGoogle Scholar
Lowy, D. R. & Willumsen, B. M. (1993). Function and regulation of Ras. Annual Review of Biochemistry 62, 851–891.CrossRefGoogle ScholarPubMed
Lu, Q., Nassar, N. & Wang, J. (2011). A mechanism of catalyzed GTP hydrolysis by Ras protein through magnesium ion. Chemical Physics Letters 516, 233–238.CrossRefGoogle Scholar
Luo, J., Loo, B. V. & Kamerlin, S. C. L. (2012a). Examining the promiscuous phosphatase activity of Pseudomonas aeruginosa arylsulfatase: a comparison to analogous phosphatases. Proteins: Structure Function and Bioinformatics 80, 1211–1226.CrossRefGoogle ScholarPubMed
Luo, J., Van Loo, B. & Kamerlin, S. C. L. (2012b). Catalytic promiscuity in Pseudomonas aeruginosa arylsulfatase as an example of chemistry-driven protein evolution. FEBS Letters 586, 1622–1630.CrossRefGoogle ScholarPubMed
Maegley, K. A., Admiral, S. J. & Herschlag, D. (1996). Ras-catalyzed hydrolysis of GTP: a new perspective from model studies. Proceedings of the National Academy of Sciences of the United States of America 93, 8160–8166.CrossRefGoogle ScholarPubMed
Manning, G., Whyte, D. B., Martinez, R., Hunter, T. & Sudarsanam, S. (2002a). The protein kinase complement of the human genome. Science 298, 1912–1934.CrossRefGoogle ScholarPubMed
Marcos, E., Field, M. J. & Creheut, R. (2010). Pentacoordinated phosphorus revisited by high-level QM/MM calculations. Proteins: Structure Function and Bioinformatics 78, 2405–2411.CrossRefGoogle ScholarPubMed
Maskill, H. (1999). Structure and Reactivity in Organic Compounds. Oxford, UK: Oxford University Press.CrossRefGoogle Scholar
Mastrangelo, I. A., Hough, P. V. C., Wall, J. S., Dodson, M., Dean, F. B. & Hurwrtz, J. (1989). ATP-dependent assembly of double hexamers of SV40T antigen at the viral origin of DNA replication. Nature 338, 658–662.CrossRefGoogle Scholar
Mayaan, E., Range, K. & York, D. M. (2004). Structure and binding of Mg(II) ions and di-metal bridge complexes with biological phosphates and phosphoranes. Journal of Biological Inorganic Chemistry: JBIC: A Publication of the Society of Biological Inorganic Chemistry 9, 807–817.CrossRefGoogle ScholarPubMed
Mccormick, F. & Wittinghofer, A. (1996). Interactions between Ras proteins and their effectors. Current Opinion in Biotechnology 7, 449–456.CrossRefGoogle ScholarPubMed
Menz, R. I., Walker, J. E. & Leslie, A. G. W. (2001). Structure of bovine mitochondrial F1-ATPase with nucleotide bound to all three catalytic sites: implications for the mechanism of rotary catalysis. Cell 106, 331–341.CrossRefGoogle ScholarPubMed
Mercero, J. M., Barrett, P., Lam, C. W., Fowler, J. E., Ugalde, J. M. & Pedersen, L. G. (2000). Quantum mechanical calculations on phosphate hydrolysis reactions. Journal of Computational Chemistry 21, 43–51.3.0.CO;2-8>CrossRefGoogle Scholar
Messer, B. M., Roca, M., Chu, Z. T., Vicatos, S., Kilshtain, A. V. & Warshel, A. (2010). Multiscale simulations of protein landscapes: using coarse-grained models as reference potentials to full explicit models. Proteins: Structure Function and Bioinformatics 78, 1212–1227.CrossRefGoogle ScholarPubMed
Milburn, M., Tong, L., Devos, A. M., Bruenger, A., Yamaizumi, Z., Nishimura, S. & Kim, S. H. (1990). Molecular switch for signal transduction: structural differences between active and inactive forms of protooncogenic Ras proteins. Science 247, 939–945.CrossRefGoogle ScholarPubMed
Mildvan, A. S. (1979). The role of metals in enzyme-catalyzed substitutions at each of the phosphorus atoms of ATP. Advances in Enzymology and Related Areas of Molecular Biology 49, 103–126.CrossRefGoogle ScholarPubMed
Mildvan, A. S. (1997). Mechanisms of signaling and related enzymes. Proteins 29, 401–416.3.0.CO;2-B>CrossRefGoogle ScholarPubMed
Mimeault, M. & Batra, S. K. (2011). Complex oncogenic signaling networks regulate brain tumor-initiating cells and their progenies: pivotal roles of wild-type EGFR, EGFRvIII mutant and hedgehog cascades and novel multitargeted therapies. Brain Pathology 21, 479–500.CrossRefGoogle ScholarPubMed
Minehardt, T., Cooke, R., Marzari, N., Car, R. & Pate, E. (2003). Car-Parrinello simulations of ATP hydrolysis in myosin. In 225th National Meeting of the American-Chemical-Society, New Orleans, LA.Google Scholar
Minehardt, T. J., Marzari, N., Cooke, R., Pate, E., Kollman, P. A. & Car, R. (2002). A classical and ab initio study of the interaction of the myosin triphosphate binding domain with ATP. Biophysical Journal 82, 660–675.CrossRefGoogle ScholarPubMed
Mlynsky, V., Banás, P., Walter, N. G., Sponer, J. & Otyepka, M. (2011). QM/MM studies of hairpin ribozyme self-cleavage suggest the feasibility of multiple competing reaction mechanisms. Journal of Physical Chemistry B 115, 13911–13924.CrossRefGoogle ScholarPubMed
Moazed, D., Robertson, J. M. & Noller, H. F. (1988). Interaction of elongation factors EF-G and EF-Tu with a conserved loop in 23S RNA. Nature 334, 362–364.CrossRefGoogle Scholar
Mohr, D., Wintermeyer, W. & Rodnina, M. V. (2002). GTPase activation of elongation factors Tu and G on the ribosome. Biochemistry 41, 12520–12528.CrossRefGoogle Scholar
Moore, P. B. (2012). How should we think about the ribosome? Annual Review of Biophysics 41, 18.11–18.19.CrossRefGoogle ScholarPubMed
More O'Ferrall, R. A. (1970). Relationships between E2 and E1cB mechanisms of β-elimination. Journal of the American Chemical Society B 274–277.CrossRefGoogle Scholar
Muegge, I., Qi, P. X., Wand, A. J., Chu, Z. T. & Warshel, A. (1997). The reorganization energy of cytochrome c revisited. Journal of Physical Chemistry B 101, 825–836.CrossRefGoogle Scholar
Muegge, I., Schweins, T., Langen, R. & Warshel, A. (1996). Electrostatic control of GTP and GDP binding in the oncoprotein p21 ras. Structure 4, 475–489.CrossRefGoogle Scholar
Muegge, I., Schweins, T. & Warshel, A. (1998). Electrostatic contributions to protein-protein binding affinities: application to Rap/Raf interaction. Proteins: Structure Function and Bioinformatics 30, 407–423.3.0.CO;2-F>CrossRefGoogle ScholarPubMed
Mukherjee, S. & Warshel, A. (2011). Electrostatic origin of the mechanochemical rotary mechanism and the catalytic dwell of F1-ATPase. Proceedings of the National Academy of Sciences of the United States of America 108, 20550–20555.CrossRefGoogle ScholarPubMed
Narlikar, G. J., Gopalakrishnan, V., Mcconnell, T. S., Usman, N. & Herschlag, D. (1995). Use of binding energy by an RNA enzyme for catalysis by positioning and substrate destabilization. Proceedings of the National Academy of Sciences of the United States of America 92, 3668–3672.CrossRefGoogle ScholarPubMed
Nassar, N., Horn, G., Herrmann, C., Block, C., Janknecht, A. & Wittinghofer, A. (1996). Ras/Rap Effector Specificity Determined by Charge Reversal. Nature Structural Biology 3, 723–729.CrossRefGoogle ScholarPubMed
Nassar, N., Horn, G., Herrmann, C., Scherer, A., Mccormick, F. & Wittinghofer, A. (1995). The 2·2 A crystal structure of the Ras-binding domain of the serine/threonine kinase c-Raf1 in complex with Rap1A and a GTP analogue. Nature 375, 554–560.CrossRefGoogle Scholar
Nikolic-Hughes, I., Rees, D. & Herschlag, D. (2004). Do electrostatic interactions with positively charged active site groups tighten the transition state for enzymatic phosphoryl transfer? Journal of the American Chemical Society 126, 11814–11819.CrossRefGoogle ScholarPubMed
Northrop, D. B. (1975). Steady-state analysis of kinetic isotope effects in enzymic reactions. Biochemistry 14, 2644–2651.CrossRefGoogle ScholarPubMed
O'brien, P. J. & Herschlag, D. (1998). Sulfatase activity of E-coli alkaline phosphatase demonstrates a functional link to arylsulfatases, an evolutionarily related enzyme family. Journal of the American Chemical Society 120, 12369–12370.CrossRefGoogle Scholar
O'brien, P. J. & Herschlag, D. (1999). Catalytic promiscuity and the evolution of new enzymatic activities. Chemistry & Biology 6, R91–R105.CrossRefGoogle ScholarPubMed
O'brien, P. J. & Herschlag, D. (2001). Functional interrelationships in the alkaline phosphatase superfamily: phosphodiesterase activity of E-coli alkaline phosphatase. Biochemistry 40, 5691–5699.CrossRefGoogle Scholar
O'Brien, P. J. & Herschlag, D. (2002). Alkaline phosphatase revisited: hydrolysis of alkyl phosphates. Biochemistry 41, 3207–3225.CrossRefGoogle ScholarPubMed
Oda, K., Matsuoka, Y., Funahashi, A. & Kitano, A. H. (2005). A comprehensive pathway map of epidermal growth factor receptor signaling. Molecular Systems Biology 1, 1–17.CrossRefGoogle ScholarPubMed
Oelschlaeger, P., Klahn, M., Beard, W. A., Wilson, S. H. & Warshel, A. (2007). Magnesium-cationic dummy atom molecules enhance representation of DNA polymerase β – in molecular dynamics simulations: improved accuracy in studies of structural features and mutational effects. Journal of Molecular Biology 366, 687–701.CrossRefGoogle ScholarPubMed
Ogle, J. M., Brodersen, D. E., Clemons, W. M. JR., Tarry, M. J., Carter, A. P., & Ramakrishnan, V. (2001). Recognition of cognate transfer RNA by the 30S ribosomal subunit. Science 292, 897–902.CrossRefGoogle ScholarPubMed
Okuno, D., Fujisawa, R., Iino, R., Hirono-Hara, Y., Imamura, H. & Nojia, H. (2008). Correlation between the conformational states of F1-ATPase as determined from its crystal structure and single-molecule rotation. Proceedings of the National Academy of Sciences of the United States of America 105, 20722–20727.CrossRefGoogle ScholarPubMed
Olguin, L. F., Askew, S. E., O'Donoghue, A. C. & Hollfelder, F. (2008). Efficient catalytic promiscuity of an enzyme superfamily: an arylsulfatase shows a rate acceleration of 1013 for phosphate monoester hydrolysis. Journal of the American Chemical Society 130, 16547–16555.CrossRefGoogle Scholar
Olsson, M. H. M., Mavri, J. & Warshel, A. (2006a). Transition state theory can be used in studies of enzyme catalysis: lessons from simulations of tunnelling and dynamical effects in lipoxygenase and other systems. Philosophical Transactions of the Royal Society B-Biological Sciences 361, 1417–1432.CrossRefGoogle ScholarPubMed
Olsson, M. H. M., Parson, W. W. & Warshel, A. (2006b). Dynamical contributions to enzyme catalysis: critical tests of a popular hypothesis. Chemical Reviews 106, 1737–1756.CrossRefGoogle ScholarPubMed
Oostenbrink, C. & Van Gunsteren, W. F. (2005). Efficient calculation of many stacking and pairing free energies in DNA from a few molecular dynamics simulations. Chemistry – A European Journal 11, 4340–4348.CrossRefGoogle ScholarPubMed
Orozco, M., Pérez, A. , Noy, A. & Luque, F. J. (2003). Theoretical methods for the simulation of nucleic acids. Chemical Society Reviews 32, 350–364.CrossRefGoogle ScholarPubMed
Pai, E. F., Krengel, U., Petsko, G. A., Goody, R. S., Kabsch, W. & Wittinghofer, A. (1990). Refined crystal structure of the triphosphate conformation of H-Ras P21 at 1·35 Å resolution: implications for the mechanism of GTP hydrolysis. The EMBO Journal 9, 2351–2359.CrossRefGoogle ScholarPubMed
Pannifer, A. D. B., Flint, A. J., Tonks, N. K. & Barford, D. (1998). Visualization of the cysteinyl-phosphate intermediate of a protein-tyrosine phosphatase by X-ray crystallography. The Journal of Biological Chemistry 273, 10454–10462.CrossRefGoogle ScholarPubMed
Pasqualato, S. & Cherfils, J. (2005). Crystallographic evidence for substrate-assisted GTP hydrolysis by a small GTP binding protein. Structure 13, 533–540.CrossRefGoogle ScholarPubMed
Patel, J. S., Branduardi, D., Masetti, M., Rocchia, W. & Cavalli, A. (2011). Insights into ligand–protein binding from local mechanical response. Journal of Chemical Theory and Computation 7, 3368–3378.CrossRefGoogle ScholarPubMed
Patel, S. S., Wong, I. & Johnson, K. A. (1991). Pre-steady-state kinetic-analysis of processive dna-replication including complete characterization of an exonuclease-deficient mutant. Biochemistry 30, 511–525.CrossRefGoogle ScholarPubMed
Pauling, L. (1960). The Nature of the Chemical Bond. Ithaca, N. Y.: Cornell University Press.Google Scholar
Pei, Z., Liu, G., Lubben, T. H. & Szczepankiewicz, B. G. (2004). Inhibition of protein tyrosine phosphatase 1B as a potential treatment of diabetes and obesity. Current Pharmaceutical Design 10, 3481–3504.CrossRefGoogle ScholarPubMed
Perreault, D. M. & Anslyn, E. V. (1997). Unifying the current data on the mechanism of cleavage – transesterification of RNA. Angewandte Chemie (International ed. in English) 36, 432–450.CrossRefGoogle Scholar
Peters, G. H., Frimurer, T. M. & Olsen, O. H. (1998). Electrostatic evaluation of the signature motif (H/V)CX5R(S/T) in protein-tyrosine phosphatases. Biochemistry 37, 5383–5393.CrossRefGoogle Scholar
Piccirilli, J. A., Vyle, J. S., Caruthers, M. G. & Cech, T. R. (1993). Metal ion catalysis in the tetrahymena ribozyme reaction. Nature 361, 85.CrossRefGoogle ScholarPubMed
Pisliakov, A. V., Cao, J., Kamerlin, S. C. L. & Warshel, A. (2009). Enzyme millisecond conformational dynamics do not catalyze the chemical step. Proceedings of the National Academy of Sciences of the United States of America 106, 17359–17364.CrossRefGoogle Scholar
Pley, H. W., Flaherty, K. M. & Mckay, D. B. (1994). Three-dimensional structure of a hammerhead ribozyme. Nature 372, 68–74.CrossRefGoogle ScholarPubMed
Plotnikov, N. V., Kamerlin, S. C. L. & Warshel, A. (2011). Paradynamics: an effective and reliable model for ab initio QM/MM free-energy calculations and related tasks. Journal of Physical Chemistry B 115, 7950–7962.CrossRefGoogle ScholarPubMed
Plotnikov, N. V. & Warshel, A. (2012). Exploring, refining and validating the paradynamics QM/MM sampling. Journal of Physical Chemistry B 116, 10342–10356.CrossRefGoogle ScholarPubMed
Post, J. R. C. B. & Ray, W. J. (1995). Reexamination of induced fit as a determinant of substrate specificity in enzymatic reactions. Biochemistry 34, 15881–15885.CrossRefGoogle ScholarPubMed
Prasad, B. R., Plotnikov, N. V. & Warshel, A. (2012). Resolving uncertainties about phosphate hydrolysis pathways by careful free energy mapping. In Press (DOI: 10.1021/jp309778n), J. Phys. Chem. B, 2012.CrossRefGoogle Scholar
Prasad, B. R. & Warshel, A. (2011). Prechemistry versus preorganization in DNA replication fidelity. Proteins: Structure Function and Bioinformatics 79, 2900–2919.CrossRefGoogle Scholar
Preiss, J. & Handler, P. (1958). Biosynthesis of diphosphopyridine nucleotide: II. Enzymatic aspects. The Journal of Biological Chemistry 233, 493–500.CrossRefGoogle ScholarPubMed
Pu, J. & Karplus, M. (2008). How subunit coupling produces the γ-subunit rotary motion in F1-ATPase. Proceedings of the National Academy of Sciences of the United States of America 105, 1192–1197.CrossRefGoogle ScholarPubMed
Pyle, A. M. (1993). Ribozymes: a distinct class of metalloenzymes. Science 261, 709.CrossRefGoogle ScholarPubMed
Radhakrishnan, R., Arora, K., Wang, Y. L., Beard, W. A., Wilson, S. H. & Schlick, T. (2006). Regulation of DNA repair fidelity by molecular checkpoints: ‘Gates’ in DNA polymerase β's substrate selected. Biochemistry 45, 15142–15156.CrossRefGoogle Scholar
Radhakrishnan, R. & Schlick, T. (2004). Orchestration of cooperative events in DNA synthesis and repair mechanism unraveled by transition path sampling of DNA polymerase β's closing. Proceedings of the National Academy of Sciences of the United States of America 101, 5970–5975.CrossRefGoogle ScholarPubMed
Radhakrishnan, R. & Schlick, T. (2005). Fidelity discrimination in DNA polymerase β: differing closing profiles for a mismatched (G: A) versus matched (G: C) base pair. Journal of the American Chemical Society 127, 13245–13252.CrossRefGoogle Scholar
Radhakrishnan, R. & Schlick, T. (2006). Correct and incorrect nucleotide incorporation pathways in DNA polymerase β. Biochemical and Biophysical Research Communications 350, 521–529.CrossRefGoogle ScholarPubMed
Radzicka, A. & Wolfenden, R. (1995). A proficient enzyme. Science 267, 90–93.CrossRefGoogle ScholarPubMed
Raines, R. T. (1998). Ribonuclease A Chemical Reviews 98, 1045–1066.CrossRefGoogle ScholarPubMed
Ramakrishnan, V. (2008). What we have learned from ribosome structures. Biochemical Society Transactions 36, 567–574.CrossRefGoogle ScholarPubMed
Ramakrishnan, V. (2010). Unraveling the structure of the ribosome (Nobel Lecture). Angewandte Chemie (International ed. in English) 49, 4355–4380.CrossRefGoogle ScholarPubMed
Riccardi, D., Konig, P., Guo, H. & Cui, Q. (2008). Proton transfer in carbonic anhydrase is controlled by electrostatics rather than the orientation of the acceptor. Biochemistry 47, 2369–2378.CrossRefGoogle Scholar
Riccardi, D., Schaefer, P. & Cui, Q. (2005). pK a calculations in solution and proteins with QM/MM free energy perturbation simulations: a quantitative test of QM/MM protocols. Journal of Physical Chemistry B 109, 17715–17733.CrossRefGoogle ScholarPubMed
Richards, F. M. & Wyckoff, H. W. (1971). In The Enzymes, vol. 4 (Ed. Boyer, P. D.), pp. 647–806. New York: Academic Press.Google Scholar
Roca, M., Vardi-Kilshtai, A. & Warshel, A. (2009). Toward accurate screening in computer aided enzyme design. Biochemistry 48, 3046–3056.CrossRefGoogle ScholarPubMed
Rodnina, M. V. & Wintermeyer, W. (2009). Recent mechanistic insights into eukaryotic ribosomes. Current Opinion in Cell Biology 21, 435–443.CrossRefGoogle ScholarPubMed
Rosta, E., Kamerlin, S. C. L. & Warshel, A. (2008). On the interpretation of the observed linear free energy relationship in phosphate hydrolysis: a thorough computational study of phosphate diester hydrolysis in solution. Biochemistry 47, 3725–3735.CrossRefGoogle ScholarPubMed
Rosta, E., Klähn, M. & Warshel, A. (2006). Towards accurate ab initio QM/MM calculations of free-energy profiles of enzymatic reactions. Journal of Physical Chemistry B 110, 2934–2941.CrossRefGoogle ScholarPubMed
Rowell, R. & Gorenstein, D. G. (1981). Multiple structure-reactivity correlations in the hydrolysis of epimeric 2-aryloxy-2-oxy-dioxaphosphorinanes. Stereoelectronic effects. Journal of the American Chemical Society 103, 5894–5902.CrossRefGoogle Scholar
Rucker, R., Oelschlaeger, P. & Warshel, A. (2009). A binding free energy decomposition approach for accurate calculations of the fidelity of DNA polymerases. Proteins: Structure Function and Bioinformatics 78, 671–680.CrossRefGoogle Scholar
Rychkova, A., Vicatos, S. & Warshel, A. (2010). On the energetics of translocon-assisted insertion of charged transmembrane helices into membranes. Proceedings of the National Academy of Sciences of the United States of America 107, 17598–17603.CrossRefGoogle ScholarPubMed
Sawaya, M. R., Prasad, R., Wilson, S. H., Kraut, J. & Pelletier, H. (1997). Crystal structures of human DNA polymerase β complexed with gapped and nicked DNA: evidence for an induced fit mechanism. Biochemistry 36, 11205–11215.CrossRefGoogle ScholarPubMed
Scarano, G., Krab, I. M., Bocchini, V. & Parmeggiani, A. (1995). Relevance of histidine-84 in the elongation-factor Tu GTPase activity and in poly(phe) synthesis – its substitution by glutamine and alanine. FEBS Letters, 365, 214–218.CrossRefGoogle ScholarPubMed
Scheffzek, K. & Ahmadian, M. (2005). GTPase activating proteins: structural and functional insights 18 years after discovery. Cellular and Molecular Life Science 62, 3014–3038.CrossRefGoogle ScholarPubMed
Scheffzek, K., Ahmadian, M. R., Kabsch, W., Wiesmuller, L., Lautwein, A., Schmitz, F. & Wittinghofer, A. (1997). The Ras-RasGAP complex – structural basis for GTPase activation and its loss in oncogenic Ras mutants. Science 277, 333–338.CrossRefGoogle ScholarPubMed
Schiemann, O., Fritscher, J., Kisseleva, N., Sigurdsson, S. T. & Prisner, T. F. (2003). Structural investigation of a high affinity MnII binding site in the hammerhead ribozyme by EPR spectroscopy and DFT calculations. Effects of neomycine-B on metal-ion bindings. Chemical & Biological Chemistry 4, 1057.CrossRefGoogle Scholar
Schmeing, T. M. & Ramakrishnan, V. (2009). What recent ribosome structures have revealed about the mechanism of translation. Nature 461, 1234–1242.CrossRefGoogle ScholarPubMed
Schmeing, T. M., Voorhees, R. M., Kelley, A. C., Gao, Y.-G., Iv, F. V. M., Weir, J. R. & Ramakrishnan, V. (2009). The crystal structure of the ribosome bound to EF-Tu and aminoacyl-tRNA. Science 326, 688–694.CrossRefGoogle ScholarPubMed
Schroeder, G. K., Lad, C., Wyman, P., Williams, N. H. & Wolfenden, R. (2006). The time required for water attack at the phosphorus atom of simple phosphodiesters and of DNA. Proceedings of the National Academy of Sciences of the United States of America 103, 4052–4055.CrossRefGoogle ScholarPubMed
Schuette, J.-C., Iv, F. V. M., Kelley, A. C., Weir, J. R., Giesebrecht, J., Connell, S. R., Loerke, J., Mielke, T., Zhang, W., Penczek, P. A., Ramakrishnan, V. & Spahn, C. M. T. (2009). GTPase activation of elongation factor EF-Tu by the ribosome during decoding. The EMBO Journal 28, 755–765.CrossRefGoogle ScholarPubMed
Schutz, C. N. & Warshel, A. (2004). The low barrier hydrogen bond (LBHB) proposal revisited: the case of the Asp … His pair in serine proteases. Proteins 55, 711–723.CrossRefGoogle ScholarPubMed
Schwans, J. P., Kraut, D. A. & Herschlag, D. (2009). Determining the catalytic role of remote substrate binding interactions in ketosteroid isomerase. Proceedings of the National Academy of Sciences of the United States of America 106, 14271–14275.CrossRefGoogle ScholarPubMed
Schweins, T. (1991). Untersuchung des reaktionsmechanismusses von ras-p21 mittels computer-modeling. Diplomarbeit Thesis, University of Southern California.Google Scholar
Schweins, T., Geyer, M., Kalbitzer, H. R., Wittinghofer, A. & Warshel, A. (1996a). Linear free energy relationships in the intrinsic and GTPase activating protein-stimulated guanosine 5′-triphosphate hydrolysis of p21 ras. Biochemistry 35, 14225–14231.CrossRefGoogle Scholar
Schweins, T., Geyer, M., Scheffzek, K., Warshel, A., Kalbitzer, H. R. & Wittinghofer, A. (1995). Substrate-assisted catalysis as a mechanism for GTP hydrolysis of p21 ras and other GTP-binding proteins. Nature Structural Biology 2, 36–44.CrossRefGoogle ScholarPubMed
Schweins, T., Langen, R. & Warshel, A. (1994). Why have mutagenesis studies not located the general base in ras p21. Nature Struct. Biol 1, 476–484.CrossRefGoogle Scholar
Schweins, T., Wittinghofer, A. & Warshel, A. (1996b). Mechanistic analysis of the observed linear free energy relationships in p21ras and related systems. Biochemistry 35, 14232–14243.CrossRefGoogle ScholarPubMed
Scott, W. G. (1999). Biophysical and biochemical investigations of RNA catalysis in the hammerhead ribozyme. Quarterly Reviews of Biophysics 32, 241–284.CrossRefGoogle ScholarPubMed
Scrima, A., Thomas, C., Deaconescu, D. & Wittinghofer, A. (2008). The Rap-RapGAP complex: GTP hydrolysis without catalytic glutamine and arginine residues. The EMBO Journal 27, 1145–1153.CrossRefGoogle ScholarPubMed
Scudder, P. H. (1990). Use of reaction cubes for generation and display of multiple mechanistic pathways. The Journal of Organic Chemistry 55, 4238–4240.CrossRefGoogle Scholar
Seewald, M. J., Körner, C., Wittinghofer, A. & Vetter, I. R. (2002). RanGAP mediates GTP hydrolysis without an arginine finger. Nature 415, 662–666.CrossRefGoogle ScholarPubMed
Seibert, E., Ross, J. B. A. & Osman, R. (2003). Contribution of opening and bending dynamics to specific recognition of DNA damage. Journal of Molecular Biology 330, 687–703.CrossRefGoogle ScholarPubMed
Sham, Y. Y., Chu, Z. T., Tao, H. & Warshel, A. (2000). Examining methods for calculations of binding free energies: LRA, LIE, PDLD-LRA, and PDLD/S-LRA calculations of ligands binding to an HIV protease. Proteins: Structure Function and Bioinformatics 39, 393–407.3.0.CO;2-H>CrossRefGoogle Scholar
Sharma, P. K., Xiang, Y., Kato, M. & Warshel, A. (2005). What are the roles of substrate assisted catalysis and proximity effects in peptide bond formation by the ribosome? Biochemistry 44, 11307–11314.CrossRefGoogle ScholarPubMed
Shimo-Kon, R., Muneyuki, E., Sakai, H., Adachi, K., Yoshida, M. & Kinosita, K. (2010). Chemo-mechanical coupling in F1-ATPase revealed by catalytic site occupancy during catalysis. Biophysical Journal 98, 1227–1236.CrossRefGoogle ScholarPubMed
Showalter, A. K., Lamarche, B. J., Bakhtina, M., Su, M. I., Tang, K. H. & Tsai, M. D. (2006). Mechanistic comparison of high-fidelity and error-prone DNA polymerases and ligases involved in DNA repair. Chemical Reviews 106, 340–360.CrossRefGoogle ScholarPubMed
Shriver, D. & Atkins, P. (2006). Inorganic Chemistry. New York: Oxford University Press.Google Scholar
Shurki, A. & Warshel, A. (2004). Why does the Ras switch ‘break’ by oncogenic mutations? Proteins: Structure Function and Bioinformatics 55, 1–10.CrossRefGoogle ScholarPubMed
Siegbahn, P. (2006). The performance of hybrid DFT for mechanisms involving transition metal complexes in enzymes. Journal of Biological Inorganic Chemistry: JBIC: A Publication of the Society of Biological Inorganic Chemistry 11, 695–701.CrossRefGoogle ScholarPubMed
Sigala, P., Kraut, D., Caaveiro, J., Pybus, B., Ruben, E., Ringe, D., Petsko, G. & Herschlag, D. (2008). Testing geometrical discrimination within an enzyme active site: constrained hydrogen bonding in the ketosteroid isomerase oxyanion hole. Journal of the American Chemical Society 130, 13696–13708.CrossRefGoogle ScholarPubMed
Simmons, D. T. (2000). SV40 large T antigen functions in DNA replication and transformation. Advances In Virus Research 55, 75–134.CrossRefGoogle ScholarPubMed
Simopoulos, T. T. & Jencks, W. P. (1994). Alkaline phosphatase is an almost perfect enzyme. Biochemistry 33, 10375–10380.CrossRefGoogle ScholarPubMed
Smith, G. K., Ke, Z., Guo, H. & Hengge, A. C. (2011). Insights into the phosphoryl transfer mechanism of cyclin-dependent protein kinases from ab initio QM/MM free-energy studies. Journal of Physical Chemistry B 115, 13713–13722.CrossRefGoogle ScholarPubMed
Smith, J. P., Brown, W. E. & Lehr, J. R. (1955). Structure of crystalline phosphoric acid. Journal of the American Chemical Society 77, 2728–2730.CrossRefGoogle Scholar
Sondek, J., Lambright, D. G., Noel, J. P., Hamm, H. E. & Sigler, P. B. (1994). GTPase mechanism of G proteins from the 1·7 Å crystal structure of transducinα-GDP-AIF−4. Nature 372, 276–279.CrossRefGoogle Scholar
Spandidos, D. A. (1989). Ras Oncogenes. New York: Plenum Press.CrossRefGoogle ScholarPubMed
Sprang, S. R. (1997a). G protein mechanisms: insights from structural analysis. Annual Review of Biochemistry 66, 639–678.CrossRefGoogle ScholarPubMed
Sprang, S. R. (1997b). G proteins, effectors and GAPs: structure and mechanism. Current Opinion in Structural Biology 7, 849–856.CrossRefGoogle ScholarPubMed
Stec, B., Holtz, K. M. & Kantrowitz, E. R. (2000a). A revised mechanism for the alkaline phosphatase reaction involving three metal ions. Journal of Molecular Biology 299, 1303–1311.CrossRefGoogle ScholarPubMed
Stec, B., Holtz, K. M. & Kantrowitz, E. R. (2000b). A revised mechanism for the alkaline phosphatase reaction involving three metal ions. Journal of Molecular Biology 299, 1303–1311.CrossRefGoogle ScholarPubMed
Steitz, T. A. (2010). From the structure and function of the ribosome to new antibiotics (Nobel Lecture). Angewandte Chemie (International ed. in English) 49, 4381–4398.CrossRefGoogle ScholarPubMed
Steitz, T. A., Smerdon, S. J., Jäger, J. & Joyce, C. M. (1994). A unified polymerase mechanism for nonhomologous DNA and RNA polymerases. Science 266, 2022–2025.CrossRefGoogle ScholarPubMed
Steitz, T. A. & Steitz, J. A. (1993). A general two-metal-ion mechanism for catalytic RNA. Proceedings of the National Academy of Sciences of the United States of America 90, 6498–6502.CrossRefGoogle ScholarPubMed
Stockbridge, R. B. & Wolfenden, R. (2009). Phosphate monoester hydrolysis in cyclohexane. Journal of the American Chemical Society 131, 18248–18249.CrossRefGoogle ScholarPubMed
Strajbl, M., Sham, Y. Y., Villa, J., Chu, Z. T. & Warshel, A. (2000). Calculation of activation entropies of chemical reactions in solution. Journal of Physical Chemistry B 104, 4578–4584.CrossRefGoogle Scholar
Štrajbl, M., Shurki, A. & Warshel, A. (2003). Converting conformational changes to electrostatic energy in molecular motors: the energetics of ATP synthase. Proceedings of the National Academy of Sciences of the United States of America 100, 14834–14839.CrossRefGoogle ScholarPubMed
Sucato, C. A., Upton, T. G., Kashemirov, B. A., Batra, V. K., Martinek, V., Xiang, Y., Beard, W. A., Pedersen, L. C., Wilson, S. H., Mckenna, C. E., Florian, J., Warshel, A. & Goodman, M. F. (2007). Modifying the β,γ leaving-group bridging oxygen alters nucleotide incorporation efficiency, fidelity, and the catalytic mechanism of DNA polymerase β. Biochemistry 46, 461–471.CrossRefGoogle ScholarPubMed
Sucato, C. A., Upton, T. G., Kashemirov, B. A., Osuna, J., Oertell, K., Beard, W. A., Wilson, S. H., Florián, J., Warshel, A., Mckenna, C. E. & Goodman, M. F. (2008). DNA polymerase β fidelity: halomethylene-modified leaving groups in pre-steady-state kinetic analysis reveal differences at the chemical transition state. Biochemistry 47, 870–879.CrossRefGoogle ScholarPubMed
Sunahara, R. K., Tesmer, J. J. G., Gilman, A. G. & Sprang, S. R. (1997). Crystal structure of the adenylyl cyclase activator Gsα. Science 278, 1943.CrossRefGoogle ScholarPubMed
Taylor, S. S. & Kornev, A. P. (2011). Protein kinases: evolution of dynamic regulatory proteins. Trends in Biochemical Sciences 36, 65–77.CrossRefGoogle ScholarPubMed
Taylor, S. S. & Radzio-Andzelm, E. (1994). Three protein kinase structures define a common motif. Structure 2, 345–355.CrossRefGoogle ScholarPubMed
Thompson, J. E., Kutateladze, T. G., Schuster, M. C., Venegas, F. D., Messmore, J. M. & Raines, R. T. (1995). Limits to catalysis by Ribonuclease A. Bioorganic Chemistry 23, 471–481.CrossRefGoogle ScholarPubMed
Tinoco, I. & Wen, J. D. (2009). Simulation and analysis of single-ribosome translation. Physical Biology 6, 10.CrossRefGoogle ScholarPubMed
Todd, A. (1959). Some aspects of phosphate chemistry. Proceedings of the National Academy of Sciences of the United States of America 45, 1389–1397.CrossRefGoogle ScholarPubMed
Tolman, R. C. (1938). The Principles of Statistical Mechanics. London, UK: Oxford University Press.Google Scholar
Topol, I. A., Cachau, R. E., Nemukhin, A. V., Grigorenko, B. L. & Burt, S. K. (2004). Quantum chemical modeling of the GTP hydrolysis by the RAS-GAP protein complex. Biochimica et Biophysica Acta – Proteins and Proteomics 1700, 125–136.CrossRefGoogle ScholarPubMed
Torres, R. A., Himo, F., Bruice, T. C., Noodleman, L. & Lovell, T. (2003). Theoretical examination of Mg2 + -mediated hydrolysis of a phosphodiester linkage as proposed for the hammerhead ribozyme. Journal of the American Chemical Society 125, 9861–9867.CrossRefGoogle ScholarPubMed
Toscano, M. D., Woycechowsky, K. J. & Hilvert, D. (2007). Minimalist active-site redesign: teaching old enzymes new tricks. Angewandte Chemie (International ed. in English) 46, 4468–4470.CrossRefGoogle ScholarPubMed
Trushkov, I. V., Zhdankin, V. V., Koz'min, A. S. & Zefirov, N. S. (1990). Cubic reaction coordinate diagram in the nucleophilic substitution process. Tetrahedron Letters 31, 3199–3200.CrossRefGoogle Scholar
Uchimaru, T., Uebayasi, M., Tanabe, K. & Taira, K. (1993). Theoretical analyses on the role of Mg2+ ions in ribozyme reactions. The FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology 7, 137.CrossRefGoogle ScholarPubMed
Van Loo, B., Jonas, S., Babtie, A. C., Benjdia, A., Berteau, O., Hyvönen, M. & Hollfelder, F. (2010). An efficient, multiply promiscuous hydrolase in the alkaline phosphatase superfamily. Proceedings of the National Academy of Sciences of the United States of America 107, 2740–2745.CrossRefGoogle ScholarPubMed
Várnai, P. & Warshel, A. (2000). Computer simulation studies of the catalytic mechanism of human aldose reductase. Journal of the American Chemical Society 122, 3849–3860.CrossRefGoogle Scholar
Vetter, I. R. & Wittinghofer, A. (1999). Nucleoside triphosphate-binding proteins: different scaffolds to achieve phosphoryl transfer. Quarterly Reviews of Biophysics 32, 1–56.CrossRefGoogle ScholarPubMed
Villa, E., Sengupta, J., Trabuco, L. G., Lebarron, J., Baxter, W. T., Shaikh, T. R., Grassucci, R. A., Nissen, P., Ehrenberg, M., Schulten, K. & Frankd, J. (2009). Ribosome-induced changes in elongation factor Tu conformation control GTP hydrolysis. Proceedings of the National Academy of Sciences of the United States of America 106, 1063–1068.CrossRefGoogle ScholarPubMed
Voorhees, R. M., Schmeing, T. M., Kelley, A. C. & Ramakrishnan, V. (2010). The mechanism for activation of GTP hydrolysis on the ribosome. Science 330, 835–838.CrossRefGoogle ScholarPubMed
Voorhees, R. M., Schmeing, T. M., Kelley, A. C. & Ramakrishnan, V. (2011). Response to comment on ‘The mechanism for activation of GTP hydrolysis on the ribosome’. Science 333, 37.CrossRefGoogle Scholar
Wang, H. & Oster, G. (1998). Energy transduction in the F1 motor of ATP synthase. Nature 396, 279–282.CrossRefGoogle ScholarPubMed
Wang, L. M., Patel, U., Ghosh, L. & Banerjee, S. (1992). DNA polymerase beta mutations in human colorectal cancer. Cancer Research 52, 4284–4827.Google ScholarPubMed
Wang, Y. & Schlick, T. (2008). Quantum mechanics/molecular mechanics investigation of the chemical reaction in Dpo4 reveals water-dependent pathways and requirements for active site reorganization. Journal of the American Chemical Society 130, 13240–13250.CrossRefGoogle ScholarPubMed
Wang, Y. N., Topol, I. A., Collins, J. R. & Burt, S. K. (2003). Theoretical studies on the hydrolysis of mono-phosphate and tri-phosphate in gas phase and aqueous solution. Journal of the American Chemical Society 125, 13265–13273.CrossRefGoogle ScholarPubMed
Warshel, A. (1978). Energetics of enzyme catalysis. Proceedings of the National Academy of Sciences of the United States of America 75, 5250–5254.CrossRefGoogle ScholarPubMed
Warshel, A. (1991). Computer Modeling of Chemical Reactions in Enzymes and Solutions. New York: John Wiley and Sons.Google Scholar
Warshel, A. (2003). Computer simulations of enzyme catalysis: methods, progress, and insights. Annual Review of Biophysics and Biomolecular Tructure 32, 425–443.CrossRefGoogle ScholarPubMed
Warshel, A., Åqvist, J. & Creighton, S. (1989). Enzymes work by Solvation substitution rather than by Desolvation. Proceedings of the National Academy of Sciences of the United States of America 86, 5820–5824.CrossRefGoogle ScholarPubMed
Warshel, A. & Florian, J. (2004). The empirical valence bond (EVB) method. In The Encyclopedia of Computational Chemistry, (Eds. von Ragué Schleyer, P., Allinger, N. L., Clark, T., Gasteiger, J., Kollman, P. A., Schaefer, H. F. III and Schreiner, P. R.), Chichester, UK: John Wiley and Sons.Google Scholar
Warshel, A., Hwang, J. K. & Åqvist, J. (1992a). Computer-simulations of enzymatic-reactions – examination of linear free-energy relationships and quantum-mechanical corrections in the initial proton-transfer step of carbonic-anhydrase. Faraday Discussions 93, 225–238.CrossRefGoogle Scholar
Warshel, A., Hwang, J. K. & Åqvist, J. (1992b). Computer simulations of enzymatic reactions: examination of linear free energy relationships and quantum mechanical corrections in the initial proton transfer step of carbonic anyhdrase. Faraday Discussions 93, 225–238.CrossRefGoogle Scholar
Warshel, A. & Papazyan, A. (1996). Energy considerations show that low-barrier hydrogen bonds do not offer a catalytic advantage over ordinary hydrogen bonds. Proceedings of the National Academy of Sciences of the United States of America 93, 13665–13670.CrossRefGoogle ScholarPubMed
Warshel, A. & Parson, W. W. (2001). Dynamics of biochemical and biophysical reactions: insight from computer simulations. Quarterly Reviews of Biophysics 34, 563–670.CrossRefGoogle ScholarPubMed
Warshel, A., Schweins, T. & Fothergill, M. (1994). Linear free energy relationships in enzymes. Theoretical analysis of the reaction of tyrosyl-tRNA synthase. Journal of the American Chemical Society 116, 8437–8442.CrossRefGoogle Scholar
Warshel, A., Sharma, P. K., Chu, Z. T. & Aqvist, J. (2007). Electrostatic contributions to binding of transition state analogues can be very different from the corresponding contributions to catalysis: phenolates binding to the oxyanion hole of ketosteroid isomerase. Biochemistry 46, 1466–1476.CrossRefGoogle Scholar
Warshel, A., Sharma, P. K., Kato, M. & Parson, W. W. (2006a). Modeling electrostatic effects in proteins. Biochimica et Biophysica Acta 1764, 1647–1676.CrossRefGoogle ScholarPubMed
Warshel, A., Sharma, P. K., Kato, M., Xiang, Y., Liu, H. & Olsson, M. H. M. (2006b). Electrostatic basis for enzyme catalysis. Chemical Reviews 106, 3210–3235.CrossRefGoogle ScholarPubMed
Warshel, A., Villà, J., Štrajbl, M. & Florián, J. (2000). Remarkable rate enhancement of orotidine 5′-monophosphate decarboxylase is due to transition state stabilization rather than ground state destabilization. Biochemistry 39, 14728–14738.CrossRefGoogle ScholarPubMed
Warshel, A. & Weiss, R. M. (1980). An empirical valence bond approach for comparing reactions in solutions and in enzymes. Journal of the American Chemical Society 102, 6218–6226.CrossRefGoogle Scholar
Weber, J. & Senior, A. E. (1997). Catalytic mechanism of F1-ATPase. Biochimica et Biophysica Acta 1319, 19–58.CrossRefGoogle ScholarPubMed
Weiss, P. M., Knight, W. B. & Cleland, W. W. (1986). Secondary 18O isotope effects on the hydrolysis of glucose 6-phosphate. Journal of the American Chemical Society 108, 2761–2762.CrossRefGoogle Scholar
Wenjin, Li., Rudack, T., Gerwert, K., Grater, F. & Schlitter, J. (2012). Exploring the Multidimensional Free Energy Surface of Phosphoester Hydrolysis with Constrained QM/MM Dynamics. Journal of Chemical Theory Computation 8, 3596–3604.Google Scholar
Westheimer, F. H. (1968). Pseudo-rotation in the hydrolysis of phosphate esters. Accounts of Chemical Research 1, 70–78.CrossRefGoogle Scholar
Westheimer, F. H. (1981). Monomeric metaphosphates. Chemical Reviews 81, 313–326.CrossRefGoogle Scholar
Westheimer, F. H. (1987). Why nature chose phosphates. Science 235, 1173–1178.CrossRefGoogle ScholarPubMed
White, S. H. & Von Heijne, G. (2008). How translocons select transmembrane helices. Annual Review of Biophysics 37, 23–42.CrossRefGoogle ScholarPubMed
Wiesmann, C., Barr, K. J., Kung, J., Zhu, J., Erlanson, D. A., Shen, W., Fahr, B. J., Zhong, M., Taylor, T., Randall, M., Mcdowell, R. S. & Hansen, S. K. (2004). Allosteric inhibition of protein tyrosine phosphatase 1B. Nature Structural and Molecular Biology 11, 730–737.CrossRefGoogle ScholarPubMed
Wiesmuller, L. & Wittinghofer, A. (1994). Signal transduction pathways involving Ras. Cellular Signalling 6, 247–267.CrossRefGoogle ScholarPubMed
Wilde, J. A., Bolton, P. H., Dell'Acqua, M., Hibler, D. W., Pourmotabbed, T. & Gerlt, J. A. (1998). Identification of residues involved in a conformational change accompanying substitutions for glutamate-43 in staphylococcal nuclease. Biochemistry 27, 4127–4132.CrossRefGoogle Scholar
Wilkie, J. & Gani, D. (1996). Comparison of inline and non-inline associative and dissociative reaction pathways for model reactions of phosphate monoester hydrolysis. Journal of the American Chemical Society, Perkin Transactions 2, 783–787.CrossRefGoogle Scholar
Williams, A. (1984). Effective charge and Leffler's Index as mechanistic tools for reactions in solution. Accounts of Chemical Research 17, 425–430.CrossRefGoogle Scholar
Williams, A. (1992). Effective charge and transition-state structure in solution. Advances in Physical Organic Chemistry 27, 1–55.Google Scholar
Williams, N. H. (2004a). Models for biological phosphoryl transfer Biochimica et Biophysica Acta 1697, 279–287.CrossRefGoogle ScholarPubMed
Williams, N. H. (2004b). Models for biological phosphoryl transfer. Biochimica et Biophysica Acta 1697, 279–287.CrossRefGoogle ScholarPubMed
Williams, N. H., Cheung, J. & Chin, J. (1998a). Reactivity of phosphate diesters doubly coordinated to a dinuclear cobalt(III) complex: dependence of the reactivity on the basicity of the leaving group. Journal of the American Chemical Society 120, 8079–8087.CrossRefGoogle Scholar
Williams, N. H., Cheung, W. & Chin, J. (1998b). Reactivity of phosphate diesters doubly coordinated to a dinuclear cobalt(III) complex: dependence of the reactivity on the basicity of the leaving group. Journal of the American Chemical Society 120, 8079–8087.CrossRefGoogle Scholar
Williams, N. H. & Wyman, P. (2001). Base catalysed phosphate diester hydrolysis. Chemical Communications 1268–1269.CrossRefGoogle Scholar
Wittinghofer, A. (2006). Phosphoryl transfer in Ras proteins, conclusive or elusive? Trends in Biochemical Sciences 31, 20–23.CrossRefGoogle ScholarPubMed
Wolf-Watz, M., Thai, V., Henzler-Wildman, K., Hadjipavlou, G., Eisenmesser, E. Z. & Kern, D. (2004). Linkage between dynamics and catalysis in a thermophilic-mesophilic enzyme pair. Nature Structural and Molecular Biology 11, 945–949.CrossRefGoogle Scholar
Wolfe-Simon, F., Blum, J. S., Kulp, T. R., Gordon, G. W., Hoeft, S. E., Pett-Ridge, J., Stolz, J. F., Webb, S. M., Weber, P. K., Davies, P. C. W., Anbar, A. D. & Oremland, R. S. (2010). A bacterium that can grow by using arsenic instead of phosphorus. Science 332, 1163–1166.CrossRefGoogle ScholarPubMed
Wolfe-Simon, F., Davies, P. C. & Anbar, A. D. (2009). Did nature also use arsenic? International Journal of Astrobiology 8, 69–74.CrossRefGoogle Scholar
Wolfenden, R. (2006). Degrees of difficulty of water-consuming reactions in the absence of enzymes. Chemical Reviews 106, 3379–3396.CrossRefGoogle ScholarPubMed
Wolfenden, R. (2011). Benchmark reaction rates, the stability of biological molecules in water, and the evolution of catalytic power in enzymes. Annual Review of Biophysics 80, 645–667.Google ScholarPubMed
Wolfenden, R., Ridgeway, C. & Young, G. (1998). Spontaneous hydrolysis of ionised phosphate monoesters and diesters and the proficiencies of the phosphatases and phosphodiesterases as catalysts. Journal of the American Chemical Society 120, 833–834.CrossRefGoogle Scholar
Wolfenden, R. & Snider, M. J. (2001). The depth of chemical time and the power of enzymes as catalysts. Accounts of Chemical Research 34, 938–945.CrossRefGoogle ScholarPubMed
Wong, K.-Y., Gu, H., Zhang, S., Piccirilli, J. A., Harris, M. E. & York, D. M. (2012). Characterization of the reaction path and transition States for RNA transphosphorylation models from theory and experiment. Angewandte Chemie (International ed. in English) 51, 647–651.CrossRefGoogle ScholarPubMed
Wong, K.-Y., Lee, T.-S. & York, D. M. (2011). Active participation of the Mg2+ ion in the reaction coordinate of RNA self-cleavage catalyzed by the hammerhead ribozyme. Journal of Chemical Theory and Computation 7, 1–3.CrossRefGoogle Scholar
Xiang, Y., Goodman, M. F., Beard, W. A., Wilson, S. H. & Warshel, A. (2008). Exploring the role of large conformational changes in the fidelity of DNA polymerase β. Proteins: Structure Function and Bioinformatics 70, 231–247.CrossRefGoogle ScholarPubMed
Xiang, Y., Oelschlaeger, P., Florian, J., Goodman, M. F. & Warshel, A. (2006). Simulating the effect of DNA polymerase mutations on transition-state energetics and fidelity: evaluating amino acid group contribution and allosteric coupling for ionized residues in human pol β. Biochemistry 45, 7036–7048.CrossRefGoogle ScholarPubMed
Yang, L. J., Beard, W. A., Wilson, S. H., Broyde, S. & Schlick, T. (2004). Highly organized but pliant active site of DNA polymerase β: compensatory mechanisms in mutant enzymes revealed by dynamics simulations and energy analyses. Biophysical Journal 86, 3392–3408.CrossRefGoogle ScholarPubMed
Yang, W., Gao, Y. Q., Cui, Q., Ma, J. & Karplus, M. (2003). The missing link between thermodynamics and structure in F1-ATPase. Proceedings of the National Academy of Sciences of the United States of America 100, 874–879.CrossRefGoogle ScholarPubMed
Yarden, Y. & Schlessinger, J. (1987). Epidermal growth factor induces rapid, reversible aggregation of the purified epidermal growth factor receptor. Biochemistry 26, 1443–1451.CrossRefGoogle ScholarPubMed
Yarus, M. (1993). How many catalytic RNAs? Ions and the Cheshire cat conjecture. The FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology 7, 31–39.CrossRefGoogle ScholarPubMed
Yonath, A. (2010). Polar bears, antibiotics, and the evolving ribosome (Nobel Lecture). Angewandte Chemie (International ed. in English) 49, 4340–4354.CrossRefGoogle ScholarPubMed
You, T. J. & Bashford, D. (1995). Conformation and hydrogen ion titration of proteins: a continuum electrostatic model with conformational flexibility. Biophysical Journal 69, 1721–1733.CrossRefGoogle ScholarPubMed
Zalatan, J. G., Fenn, T. D., Brunger, T. A. & Herschlag, D. (2006). Structural and functional comparisons of nucleotide pyrophosphate/phosphodiesterase and alkaline phosphatase: implications for mechanism and evolution. Biochemistry 45, 9788–9803.CrossRefGoogle Scholar
Zalatan, J. G. & Herschlag, D. (2006). Alkaline phosphatases mono- and diesterase reactions: comparative transition state analysis. Journal of the American Chemical Society 128, 1293–1303.CrossRefGoogle ScholarPubMed
Zeidler, W., Egle, C., Ribeiro, S., Wagner, A., Katunin, V., Kreutzer, R., Rodnina, M., Wintermeyer, W. & Sprinzl, M. (1995). Site-directed mutagenesis of Thermus thermophilus elongation factor Tu – replacement of His85, Asp81 and Arg300. European Journal of Biochemistry 229, 596–604.Google ScholarPubMed
Zhang, H., Zha, X., Tan, Y., Hornbeck, P. V., Mastrangelo, A. J., Alessi, D. R., Polakiewicz, R. D. & Comb, M. J. (2002). Phosphoprotein analysis using antibodies broadly reactive against phosphorylated motifs. The Journal of Biological Chemistry 277, 39379–39387.CrossRefGoogle ScholarPubMed
Zhang, Z.-Y. (2003). Chemical and mechanistic approaches to the study of protein tyrosine phosphatases. Accounts of Chemical Research 36, 385–392.CrossRefGoogle Scholar
Zhang, Z. Y., Harms, E. & Van Etten, R. L. (1994). Asp129 of low molecular weight protein tyrosine phosphatase is involved in leaving group protonation. The Journal of Biological Chemistry 269, 25947–25950.CrossRefGoogle ScholarPubMed
Zhang, Z. Y., Wang, Y. & Dixon, J. E. (1999). Dissecting the catalytic mechanism of protein-tyrosine phosphatases. Proceedings of the National Academy of Sciences of the United States of America 91, 1624–1627.CrossRefGoogle Scholar
Zhou, D.-M., Kumar, P. K. R., Zhang, L.-H. & Taira, K. (1996). Ribozyme mechanism revisited: evidence against direct coordination of a Mg2+ ion with the Pro-R oxygen if the scissile phosphate in the transition state of a hammerhead ribizyme-catalyzed reaction. In EMBO Workshop, Xanten, Germany.Google Scholar
Zhou, D.-M. & Taira, K. (1998). The hydrolysis of RNA: from theoretical calculations to the hammerhead ribozyme-mediated cleavage of RNA. Chemical Reviews 98, 991–1026.CrossRefGoogle Scholar