title: Galactose-binding site in Escherichia coli heat-labile enterotoxin (LT) and cholera toxin (CT).
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.
authors.affiliation: Department of Biological Structure SM-20, University of Washington, Seattle 98195.
authors.forename: E A
authors.initials: EA
authors.lastname: Merritt
authors.forename: T K
authors.initials: TK
authors.lastname: Sixma
authors.forename: K H
authors.initials: KH
authors.lastname: Kalk
authors.forename: B A
authors.initials: BA
authors.lastname: van Zanten
authors.forename: W G
authors.initials: WG
authors.lastname: Hol
mesh_terms: D001427:Bacterial Toxins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002135:Calcium-Binding Proteins; D002240:Carbohydrate Sequence; D002352:Carrier Proteins / Q000737:chemistry; D002772:Cholera Toxin / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D015195:Drug Design; D004768:Enterotoxins / Q000737:chemistry* / Q000378:metabolism; D029968:Escherichia coli Proteins; D005690:Galactose / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins; D033902:Periplasmic Binding Proteins; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry
chemical_list: D001427:Bacterial Toxins; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D009004:Monosaccharide Transport Proteins; D033902:Periplasmic Binding Proteins; C023550:galactose-binding protein; D014867:Water; D002772:Cholera Toxin; C027538:heat-labile enterotoxin, E coli; D005690:Galactose