2XRS

Crystal structures exploring the origins of the broader specificity of escherichia coli heat-labile enterotoxin compared to cholera toxin

Summary for 2XRS

• Entry DOI: 10.2210/pdb2xrs/pdb
• Related: 1DJR 1EEF 1EFI 1FD7 1HTL 1JQY 1LT3 1LT4 1LT5 1LT6 1LTA 1LTB 1LTG 1LTI 1LTS 1LTT 1PZI 2XRQ
• Descriptor: HEAT-LABILE ENTEROTOXIN B CHAIN, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-3)-beta-D-galactopyranose, ... (5 entities in total)
• Functional Keywords: toxin, host-pathogen interactions, molecular recognition, protein-carbohydrate interaction
• Biological source: ESCHERICHIA COLI
• Total number of polymer chains: 10
• Total formula weight: 122029.97

Authors

Holmner, A.,Mackenzie, A.,Okvist, M.,Jansson, L.,Lebens, M.,Teneberg, S.,Krengel, U. (deposition date: 2010-09-20, release date: 2010-12-08, Last modification date: 2023-12-20)

Primary citation

Holmner, A.,Mackenzie, A.,Okvist, M.,Jansson, L.,Lebens, M.,Teneberg, S.,Krengel, U.
Crystal Structures Exploring the Origins of the Broader Specificity of Escherichia Coli Heat-Labile Enterotoxin Compared to Cholera Toxin
J.Mol.Biol., 406:387-, 2011

PubMed Abstract: Cholera toxin (CT) and Escherichia coli heat-labile enterotoxin (LT) are structurally and functionally related and share the same primary receptor, the GM1 ganglioside. Despite their extensive similarities, these two toxins exhibit distinct ligand specificities, with LT being more promiscuous than CT. Here, we have attempted to rationalize the broader binding specificity of LT and the subtle differences between the binding characteristics of LTs from human and porcine origins (mediated by their B subunit pentamers, hLTB and pLTB, respectively). The analysis is based on two crystal structures of pLTB in complexes with the pentasaccharide of its primary ligand, GM1, and with neolactotetraose, the carbohydrate determinant of a typical secondary ligand of LTs, respectively. Important molecular determinants underlying the different binding specificities of LTB and CTB are found to be contributed by Ser95, Tyr18 and Thr4 (or Ser4 of hLTB), which together prestabilize the binding site by positioning Lys91, Glu51 and the adjacent loop region (50-61) containing Ile58 for ligand binding. Glu7 and Ala1 may also play an important role. Many of these residues are closely connected with a recently identified second binding site, and there appears to be cross-talk between the two sites. Binding to N-acetyllactosamine-terminated receptors is further augmented by Arg13 (present in pLT and some hLT variants), as previously predicted.

PubMed: 21168418
DOI: 10.1016/J.JMB.2010.11.060

Experimental method

X-RAY DIFFRACTION (1.81 Å)