1UWU

Structure of beta-glycosidase from Sulfolobus solfataricus in complex with D-glucohydroximo-1,5-lactam


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.194 

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This is version 1.3 of the entry. See complete history


Literature

Structural studies of the beta-glycosidase from Sulfolobus solfataricus in complex with covalently and noncovalently bound inhibitors.

Gloster, T.M.Roberts, S.Ducros, V.M.Perugino, G.Rossi, M.Hoos, R.Moracci, M.Vasella, A.Davies, G.J.

(2004) Biochemistry 43: 6101-6109

  • DOI: https://doi.org/10.1021/bi049666m
  • Primary Citation of Related Structures:  
    1UWQ, 1UWR, 1UWS, 1UWT, 1UWU

  • PubMed Abstract: 

    Transition-state mimicry is increasingly important both to understand enzyme mechanism and to direct the synthesis of putative therapeutic agents. X-ray crystallography is able to provide vital information on the interactions between an enzyme and the potential inhibitor. Here we report the structures, at approximately 2 A resolution, of a family GH1 beta-glycosidase from the hyperthermophilic archaeon Sulfolobus solfataricus, in complex with both covalently (derived from 2-fluoro-glycosides) and noncovalently (hydroximolactam) bound inhibitors. The enzyme has broad specificity, accommodating both gluco- and galacto-configured substrates, and the crystallographic data demonstrate that the only difference in the way these ligands bind lies in the interactions between Gln18, Glu432, and Trp433, and the hydroxyl group at the O3 and O4 positions. Inhibition by the differently configured ligands was also shown to be extremely similar, with K(i) values of 1.04 and 1.08 microM for the gluco and galacto epimers, respectively. The noncovalently bound inhibitors have a trigonal anomeric carbon, adopt a (4)H(3) (half-chair) conformation, and an interaction is formed between O2 and the catalytic nucleophile, all of which contribute to (partial) mimicry of the oxocarbenium-ion-like transition state. The inhibition of the beta-glycosidase from S. solfataricus by hydroximolactams is discussed in light of the emerging work on family GH1 glycosidase inhibition by a spectrum of putative transition-state mimics.


  • Organizational Affiliation

    Structural Biology Laboratory, Department of Chemistry, The University of York, Heslington, York YO10 5YW, United Kingdom.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
BETA-GALACTOSIDASE
A, B
489Saccharolobus solfataricusMutation(s): 0 
EC: 3.2.1.23
UniProt
Find proteins for P22498 (Saccharolobus solfataricus (strain ATCC 35092 / DSM 1617 / JCM 11322 / P2))
Explore P22498 
Go to UniProtKB:  P22498
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP22498
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
GOX Binding MOAD:  1UWU Ki: 1040 (nM) from 1 assay(s)
PDBBind:  1UWU Ki: 1040 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.194 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 168.036α = 90
b = 168.036β = 90
c = 95.742γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-05-20
    Type: Initial release
  • Version 1.1: 2015-04-15
    Changes: Database references, Derived calculations, Non-polymer description, Other, Structure summary, Version format compliance
  • Version 1.2: 2018-02-28
    Changes: Database references, Source and taxonomy
  • Version 1.3: 2023-12-13
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description