Novel Binding Site Identified in a Hybrid between Cholera Toxin and Heat- Labile Enterotoxin 1.9 Aa Crystal Structure Reveals the Details

A hybrid between the B subunits of cholera toxin and Escherichia coli heat-labile enterotoxin has been described, which exhibits a novel binding specificity to blood group A and B type 2 determinants. In the present investigation, we have determined the crystal structure of this protein hybrid, term...

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Bibliographic Details
Published in:Structure (London) 2004-09, Vol.12 (9), p.1655-1667
Main Authors: Holmner, A, Lebens, M, Teneberg, S, Aangstroem, J, Oekvist, M, Krengel, U
Format: Article
Language:English
Subjects:
Escherichia coli
Vibrio cholerae
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Summary:A hybrid between the B subunits of cholera toxin and Escherichia coli heat-labile enterotoxin has been described, which exhibits a novel binding specificity to blood group A and B type 2 determinants. In the present investigation, we have determined the crystal structure of this protein hybrid, termed LCTBK, in complex with the blood group A pentasaccharide GalNAc alpha 3(Fuc alpha 2)Gal beta 4(Fuc alpha 3)GlcNAc beta , confirming not only the novel binding specificity but also a distinct new oligosaccharide binding site. Binding studies revealed that the new specificity can be ascribed to a single mutation (S4N) introduced into the sequence of Escherichia coli heat-labile enterotoxin. At a resolution of 1.9 Aa, the new binding site is resolved in excellent detail. Main features include a complex network of water molecules, which is well preserved by the parent toxins, and an unexpectedly modest contribution to binding by the critical residue Asn4, which interacts with the ligand only via a single water molecule.
ISSN:0969-2126
DOI:10.1016/j.str.2004.06.022