2XRQ

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.213 

wwPDB Validation   3D Report Full Report


This is version 2.1 of the entry. See complete history


Literature

Crystal Structures Exploring the Origins of the Broader Specificity of Escherichia Coli Heat-Labile Enterotoxin Compared to Cholera Toxin

Holmner, A.Mackenzie, A.Okvist, M.Jansson, L.Lebens, M.Teneberg, S.Krengel, U.

(2011) J Mol Biol 406: 387

  • DOI: https://doi.org/10.1016/j.jmb.2010.11.060
  • Primary Citation of Related Structures:  
    2XRQ, 2XRS

  • 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.


  • Organizational Affiliation

    Department of Chemistry, University of Oslo, P.O. Box 1033 Blindern, NO-0315 Oslo, Norway. asa.holmner-rocklov@vll.se


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HEAT-LABILE ENTEROTOXIN B CHAINA [auth D],
B [auth E],
C [auth F],
D [auth G],
E [auth H]
103Escherichia coliMutation(s): 0 
UniProt
Find proteins for P32890 (Escherichia coli)
Explore P32890 
Go to UniProtKB:  P32890
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP32890
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
beta-D-galactopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-galactopyranose-(1-4)-[N-acetyl-alpha-neuraminic acid-(2-3)]beta-D-galactopyranose-(1-4)-beta-D-glucopyranoseF [auth A],
G [auth B],
H [auth C],
I,
J
5N/A
Glycosylation Resources
GlyTouCan:  G48558GR
GlyCosmos:  G48558GR
GlyGen:  G48558GR
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.213 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 112.009α = 90
b = 96.099β = 97.22
c = 66.289γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-12-08
    Type: Initial release
  • Version 1.1: 2012-06-06
    Changes: Database references, Version format compliance
  • Version 1.2: 2015-04-01
    Changes: Database references
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Other, Structure summary
  • Version 2.1: 2023-12-20
    Changes: Data collection, Database references, Refinement description, Structure summary