Abstract
Clostridium difficile TcdA is a large toxin that binds carbohydrates on intestinal epithelial cells. A 2-A resolution cocrystal structure reveals two molecules of alpha-Gal-(1,3)-beta-Gal-(1,4)-beta-GlcNAcO(CH(2))(8)CO(2)CH(3) binding in an extended conformation to TcdA. Residues forming key contacts with the trisaccharides are conserved in all seven putative binding sites in TcdA, suggesting a mode of multivalent binding that may be exploited for the rational design of novel therapeutics.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Bacterial Toxins / chemistry*
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Bacterial Toxins / metabolism*
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Carbohydrate Metabolism*
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Carbohydrates / chemistry*
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Clostridioides difficile / chemistry*
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Clostridioides difficile / metabolism*
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Enterotoxins / chemistry*
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Enterotoxins / metabolism*
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Hydrogen Bonding
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Models, Molecular
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Protein Binding
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Protein Structure, Tertiary
Substances
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Bacterial Toxins
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Carbohydrates
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Enterotoxins
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tcdA protein, Clostridium difficile