title: Structure of partially-activated E. coli heat-labile enterotoxin (LT) at 2.6 A resolution.
abstract: Biological toxicity of E. coli heat-labile enterotoxin and the closely related cholera toxin requires that the assembled toxin be activated by proteolytic cleavage of the A subunit and reduction of a disulfide bond internal to the A subunit. The structural role served by this reduction and cleavage is not known, however. We have crystallographically determined the structure of the E. coli heat-labile enterotoxin AB5 hexamer in which the A subunit has been cleaved by trypsin between residues 192 and 195. The toxin is thus partially activated, in that it has been cleaved but the disulfide bond has not been reduced. The structure of the A subunit in the cleaved toxin is substantially the same as that previously observed for the uncleaved AB5 structure, suggesting that although such cleavage is required for biological activity of the toxin it does not by itself cause a conformational change.
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: S E
authors.initials: SE
authors.lastname: Pronk
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: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D001427:Bacterial Toxins / Q000737:chemistry*; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D004220:Disulfides / Q000378:metabolism; D004768:Enterotoxins / Q000737:chemistry*; D004926:Escherichia coli / Q000737:chemistry*; D029968:Escherichia coli Proteins; D046911:Macromolecular Substances; D011487:Protein Conformation; D013816:Thermodynamics; D014357:Trypsin / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D004220:Disulfides; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D046911:Macromolecular Substances; D000246:Adenosine Diphosphate Ribose; C027538:heat-labile enterotoxin, E coli; D014357:Trypsin