Journal article
Structure of streptococcal pyrogenic exotoxin A reveals a novel metal cluster
Protein science, Vol.9(9), pp.1847-1851
09/2000
DOI: 10.1110/ps.9.9.1847
PMCID: PMC2144691
PMID: 11045630
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).
Details
- Title: Subtitle
- Structure of streptococcal pyrogenic exotoxin A reveals a novel metal cluster
- Creators
- Cathleen A EarhartGregory M VathManuela Roggiani - Department of Microbiology, University of Minnesota Medical School, Box 196 UMHC, Minneapolis, Minnesota 55455Patrick M Schlievert - Department of Microbiology, University of Minnesota Medical School, Box 196 UMHC, Minneapolis, Minnesota 55455Douglas H Ohlendorf
- Resource Type
- Journal article
- Publication Details
- Protein science, Vol.9(9), pp.1847-1851
- Publisher
- Cambridge University Press
- DOI
- 10.1110/ps.9.9.1847
- PMID
- 11045630
- PMCID
- PMC2144691
- ISSN
- 0961-8368
- eISSN
- 1469-896X
- Number of pages
- 5
- Language
- English
- Date published
- 09/2000
- Academic Unit
- Microbiology and Immunology; Internal Medicine
- Record Identifier
- 9984001151502771
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