1PL8

human SDH/NAD+ complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.222 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.195 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

X-ray crystallographic and kinetic studies of human sorbitol dehydrogenase.

Pauly, T.A.Ekstrom, J.L.Beebe, D.A.Chrunyk, B.Cunningham, D.Griffor, M.Kamath, A.Lee, S.E.Madura, R.Mcguire, D.Subashi, T.Wasilko, D.Watts, P.Mylari, B.L.Oates, P.J.Adams, P.D.Rath, V.L.

(2003) Structure 11: 1071-1085

  • DOI: https://doi.org/10.1016/s0969-2126(03)00167-9
  • Primary Citation of Related Structures:  
    1PL6, 1PL7, 1PL8

  • PubMed Abstract: 

    Sorbitol dehydrogenase (hSDH) and aldose reductase form the polyol pathway that interconverts glucose and fructose. Redox changes from overproduction of the coenzyme NADH by SDH may play a role in diabetes-induced dysfunction in sensitive tissues, making SDH a therapeutic target for diabetic complications. We have purified and determined the crystal structures of human SDH alone, SDH with NAD(+), and SDH with NADH and an inhibitor that is competitive with fructose. hSDH is a tetramer of identical, catalytically active subunits. In the apo and NAD(+) complex, the catalytic zinc is coordinated by His69, Cys44, Glu70, and a water molecule. The inhibitor coordinates the zinc through an oxygen and a nitrogen atom with the concomitant dissociation of Glu70. The inhibitor forms hydrophobic interactions to NADH and likely sterically occludes substrate binding. The structure of the inhibitor complex provides a framework for developing more potent inhibitors of hSDH.


  • Organizational Affiliation

    Exploratory Medicinal Sciences, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
human sorbitol dehydrogenase
A, B, C, D
356Homo sapiensMutation(s): 0 
EC: 1.1.1.14
UniProt & NIH Common Fund Data Resources
Find proteins for Q00796 (Homo sapiens)
Explore Q00796 
Go to UniProtKB:  Q00796
PHAROS:  Q00796
GTEx:  ENSG00000140263 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ00796
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.222 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.195 
  • Space Group: P 62
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 133.776α = 90
b = 133.776β = 90
c = 224.708γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
CNSphasing

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2004-02-17
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2024-02-14
    Changes: Data collection, Database references, Derived calculations