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New developments in probing and targeting protein acylation in malaria, leishmaniasis and African sleeping sickness

Published online by Cambridge University Press:  08 March 2017

MARKUS RITZEFELD Open the ORCID record for MARKUS RITZEFELD [Opens in a new window] ,
MEGAN H. WRIGHT  and
EDWARD W. TATE
MARKUS RITZEFELD
Affiliation:
Department of Chemistry, Imperial College London, London SW7 2AZ, UK
MEGAN H. WRIGHT
Affiliation:
School of Chemistry, University of Leeds, Leeds LS2 9JT, UK
EDWARD W. TATE*
Affiliation:
Department of Chemistry, Imperial College London, London SW7 2AZ, UK
*
*Corresponding author: Department of Chemistry, Imperial College London, London SW7 2AZ, UK. E-mail: [email protected]
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Summary

Infections by protozoan parasites, such as Plasmodium falciparum or Leishmania donovani, have a significant health, social and economic impact and threaten billions of people living in tropical and sub-tropical regions of developing countries worldwide. The increasing range of parasite strains resistant to frontline therapeutics makes the identification of novel drug targets and the development of corresponding inhibitors vital. Post-translational modifications (PTMs) are important modulators of biology and inhibition of protein lipidation has emerged as a promising therapeutic strategy for treatment of parasitic diseases. In this review we summarize the latest insights into protein lipidation in protozoan parasites. We discuss how recent chemical proteomic approaches have delivered the first global overviews of protein lipidation in these organisms, contributing to our understanding of the role of this PTM in critical metabolic and cellular functions. Additionally, we highlight the development of new small molecule inhibitors to target parasite acyl transferases.

Keywords

acyl transferasepalmitoylationpost-translational modificationprotozoan parasitesprotein lipidationsmall molecule inhibitorproteomicsNMTN-myristoyl transferase
Type
Special Issue Review
Information
Parasitology , Volume 145 , Special Issue 2: Microbial protein targets: towards understanding and intervention , February 2018 , pp. 157 - 174
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Copyright
Copyright © Cambridge University Press 2017 

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Footnotes

†

Authors contributed equally to this manuscript.

References

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