1XDW

NAD+-dependent (R)-2-Hydroxyglutarate Dehydrogenase from Acidaminococcus fermentans


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.98 Å
  • R-Value Free: 0.225 
  • R-Value Work: 0.177 
  • R-Value Observed: 0.180 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structural basis for stereo-specific catalysis in NAD(+)-dependent (R)-2-hydroxyglutarate dehydrogenase from Acidaminococcus fermentans.

Martins, B.M.Macedo-Ribeiro, S.Bresser, J.Buckel, W.Messerschmidt, A.

(2005) FEBS J 272: 269-281

  • DOI: https://doi.org/10.1111/j.1432-1033.2004.04417.x
  • Primary Citation of Related Structures:  
    1XDW

  • PubMed Abstract: 

    NAD(+)-dependent (R)-2-hydroxyglutarate dehydrogenase (HGDH) catalyses the reduction of 2-oxoglutarate to (R)-2-hydroxyglutarate and belongs to the d-2-hydroxyacid NAD(+)-dependent dehydrogenase (d-2-hydroxyacid dehydrogenase) protein family. Its crystal structure was determined by phase combination to 1.98 A resolution. Structure-function relationships obtained by the comparison of HGDH with other members of the d-2-hydroxyacid dehydrogenase family give a chemically satisfying view of the substrate stereoselectivity and catalytic requirements for the hydride transfer reaction. A model for substrate recognition and turnover is discussed. The HGDH active site architecture is structurally optimized to recognize and bind the negatively charged substrate 2-oxoglutarate. The structural position of the side chain of Arg52, and its counterparts in other family members, strongly correlates with substrate specificity towards substitutions at the C3 atom (linear or branched substrates). Arg235 interacts with the substrate's alpha-carboxylate and carbonyl groups, having a dual role in both substrate binding and activation, and the gamma-carboxylate group can dock at an arginine cluster. The proton-relay system built up by Glu264 and His297 permits His297 to act as acid-base catalyst and the 4Re-hydrogen from NADH is transferred as hydride to the carbonyl group Si-face leading to the formation of the correct enantiomer (R)-2-hydroxyglutarate.


  • Organizational Affiliation

    MPI Biochemie, Strukturforschung, Martinsried, Germany. messersc@biochem.mpg.de


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
NAD+-dependent (R)-2-Hydroxyglutarate Dehydrogenase331Acidaminococcus fermentansMutation(s): 0 
Gene Names: hgh
EC: 1.1.1
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.98 Å
  • R-Value Free: 0.225 
  • R-Value Work: 0.177 
  • R-Value Observed: 0.180 
  • Space Group: P 61 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 67.49α = 90
b = 67.49β = 90
c = 312.785γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
XDSdata scaling
SHARPphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-03-08
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2024-02-14
    Changes: Data collection, Database references