Abstract
The galactose-binding site in cholera toxin and the closely related heat-labile enterotoxin (LT) from Escherichia coli is an attractive target for the rational design of potential anti-cholera drugs. In this paper we analyse the molecular structure of this binding site as seen in several crystal structures, including that of an LT:galactose complex which we report here at 2.2 A resolution. The binding surface on the free toxin contains several tightly associated water molecules and a relatively flexible loop consisting of residues 51-60 of the B subunit. During receptor binding this loop becomes tightly ordered by forming hydrogen bonds jointly to the GM1 pentasaccharide and to a set of water molecules which stabilize the toxin:receptor complex.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Bacterial Toxins / chemistry*
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Bacterial Toxins / metabolism
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Binding Sites
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Calcium-Binding Proteins*
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Carbohydrate Sequence
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Carrier Proteins / chemistry
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Cholera Toxin / chemistry*
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Cholera Toxin / metabolism
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Crystallography, X-Ray
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Drug Design
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Enterotoxins / chemistry*
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Enterotoxins / metabolism
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Escherichia coli Proteins*
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Galactose / chemistry*
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Galactose / metabolism
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Hydrogen Bonding
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Models, Molecular
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Molecular Sequence Data
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Monosaccharide Transport Proteins*
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Periplasmic Binding Proteins*
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Protein Conformation
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Structure-Activity Relationship
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Water / chemistry
Substances
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Bacterial Toxins
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Calcium-Binding Proteins
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Carrier Proteins
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Enterotoxins
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Escherichia coli Proteins
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Monosaccharide Transport Proteins
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Periplasmic Binding Proteins
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galactose-binding protein
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Water
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Cholera Toxin
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heat-labile enterotoxin, E coli
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Galactose