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Structure of streptococcal pyrogenic exotoxin A reveals a novel metal cluster

Published online by Cambridge University Press:  05 October 2000

MANUELA ROGGIANI
Affiliation:
Department of Microbiology, University of Minnesota Medical School, Box 196 UMHC, Minneapolis, Minnesota 55455
PATRICK M. SCHLIEVERT
Affiliation:
Department of Microbiology, University of Minnesota Medical School, Box 196 UMHC, Minneapolis, Minnesota 55455
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Abstract

The streptococcal pyrogenic toxins A, B, and C (SPEA, SPEB, and SPEC) are responsible for the fever, rash, and other toxicities associated with scarlet fever and streptococcal toxic shock syndrome. This role, together with the ubiquity of diseases caused by Streptococcus pyogenes, have prompted structural analyses of SPEA by several groups. Papageorgiou et al. (1999) have recently reported the structure of SPEA crystallized in the absence of zinc. Zinc has been shown to be important in the ability of some staphylococcal and streptococcal toxins to stimulate proliferation of CD4+ T-cells. Since cadmium is more electron dense than zinc and typically binds interchangeably, we grew crystals in the presence of 10 mM CdCl2. Crystals have been obtained in three space groups, and the structure in the P212121 crystal form has been refined to 1.9 Å resolution. The structural analysis revealed an identical tetramer as well as a novel tetrahedral cluster of cadmium in all three crystal forms on a disulfide loop encompassing residues 87–98. No cadmium was bound at the site homologous to the zinc site in staphylococcal enterotoxins C (SECs) despite the high structural homology between SPEA and SECs. Subsequent soaking of crystals grown in the presence of cadmium in 10 mM ZnCl2 showed that zinc binds in this site (indicating it can discriminate between zinc and cadmium ions) using the three ligands (Asp77, His106, and His110) homologous to the SECs plus a fourth ligand (Glu33).

Type
FOR THE RECORD
Copyright
2000 The Protein Society

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