Premium
Structure of streptococcal pyrogenic exotoxin A reveals a novel metal cluster
Author(s) -
Earhart Cathleen A.,
Vath Gregory M.,
Roggiani Manuela,
Schlievert Patrick M.,
Ohlendorf Douglas H.
Publication year - 2000
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.9.9.1847
Subject(s) - zinc , cadmium , tetramer , chemistry , toxic shock syndrome , streptococcus pyogenes , stereochemistry , crystallography , microbiology and biotechnology , staphylococcus aureus , biology , biochemistry , bacteria , genetics , organic chemistry , enzyme
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 CdCl 2 . Crystals have been obtained in three space groups, and the structure in the P2 1 2 1 2 1 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 ZnCl 2 showed that zinc binds in this site (indicating it can discriminate between zinc and cadmium ions) using the three ligands (Asp77, His106, and His 110) homologous to the SECs plus a fourth ligand (Glu33).