1E5J

ENDOGLUCANASE CEL5A FROM BACILLUS AGARADHAERENS IN THE TETRAGONAL CRYSTAL FORM IN COMPLEX WITH METHYL-4II-S-ALPHA-CELLOBIOSYL-4II-THIO-BETA-CELLOBIOSIDE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.222 
  • R-Value Work: 0.177 
  • R-Value Observed: 0.179 

wwPDB Validation   3D Report Full Report


This is version 2.0 of the entry. See complete history


Literature

Mixed-Linkage Cellooligosaccharides: A New Class of Glycoside Hydrolase Inhibitors

Fort, S.Varrot, A.Schulein, M.Cottaz, S.Driguez, H.Davies, G.J.

(2001) Chembiochem 2: 319

  • DOI: https://doi.org/10.1002/1439-7633(20010504)2:5<319::AID-CBIC319>3.0.CO;2-Q
  • Primary Citation of Related Structures:  
    1E5J

  • PubMed Abstract: 

    A new class of inhibitors for beta-D-glycoside hydrolases, in which a single alpha-(1-->4)-glycosidic bond is incorporated into an otherwise all-beta-(1-->4)-linked oligosaccharide, is described. Such mixed beta/alpha-linkage cellooligosaccharides are not transition-state mimics, but instead are capable of utilising binding energy from numerous subsites, spanning either side of the catalytic centre, without the need for substrate distortion. This binding is significant; a mixed alpha/beta-D-tetrasaccharide acts competitively on a number of cellulases, displaying inhibition constants in the range of 40-300 microM. Using the Bacillus agaradhaerens enzyme Cel5A as a model system, one such mixed beta/alpha-cellooligosaccharide, methyl 4(II),4(III)-dithio-alpha-cellobiosyl-(1-->4)-beta-cellobioside, displays a K(i) value of 100 microM, an inhibition at least 150 times better than is observed with an equivalent all-beta-linked compound. The three-dimensional structure of B. agaradhaerens Cel5A in complex with methyl 4(II),4(III)-dithio-alpha-cellobiosyl-(1-->4)-beta-cellobioside has been determined at 1.8 A resolution. This confirms the expected mode of binding in which the ligand, with all four pyranosides in the (4)C(1) chair conformation, occupies the -3, -2 and +1 subsites whilst evading the catalytic (-1) subsite. Such "by-pass" compounds offer great scope for the development of a new class of beta-D-glycoside hydrolase inhibitors.


  • Organizational Affiliation

    Centre de Recherches sur les Macromolécules Végétales (CERMAV-CNRS), Affiliated with Université Joseph Fourier, Grenoble B.P. 53, 38041 Grenoble cedex 9, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ENDOGLUCANASE 5A305Salipaludibacillus agaradhaerensMutation(s): 0 
EC: 3.2.1.4
UniProt
Find proteins for O85465 (Salipaludibacillus agaradhaerens)
Explore O85465 
Go to UniProtKB:  O85465
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO85465
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-glucopyranose-(1-4)-4-thio-beta-D-glucopyranose-(1-4)-4-thio-beta-D-glucopyranose-(1-4)-methyl beta-D-glucopyranoside
B
4N/AN/A
Glycosylation Resources
GlyTouCan:  G15528LD
GlyCosmos:  G15528LD
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.222 
  • R-Value Work: 0.177 
  • R-Value Observed: 0.179 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 74.52α = 90
b = 74.52β = 90
c = 136.193γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2001-07-26
    Type: Initial release
  • Version 1.1: 2012-11-28
    Changes: Database references, Derived calculations, Non-polymer description, Other, Source and taxonomy, Structure summary, Version format compliance
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Other, Structure summary