3GQT

Crystal structure of glutaryl-CoA dehydrogenase from Burkholderia pseudomallei with fragment (1,4-dimethyl-1,2,3,4-tetrahydroquinoxalin-6-yl)methylamine


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.99 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.202 

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This is version 1.3 of the entry. See complete history


Literature

Probing conformational states of glutaryl-CoA dehydrogenase by fragment screening.

Begley, D.W.Davies, D.R.Hartley, R.C.Hewitt, S.N.Rychel, A.L.Myler, P.J.Van Voorhis, W.C.Staker, B.L.Stewart, L.J.

(2011) Acta Crystallogr Sect F Struct Biol Cryst Commun 67: 1060-1069

  • DOI: https://doi.org/10.1107/S1744309111014436
  • Primary Citation of Related Structures:  
    3D6B, 3EOM, 3EON, 3GNC, 3GQT

  • PubMed Abstract: 

    Glutaric acidemia type 1 is an inherited metabolic disorder which can cause macrocephaly, muscular rigidity, spastic paralysis and other progressive movement disorders in humans. The defects in glutaryl-CoA dehydrogenase (GCDH) associated with this disease are thought to increase holoenzyme instability and reduce cofactor binding. Here, the first structural analysis of a GCDH enzyme in the absence of the cofactor flavin adenine dinucleotide (FAD) is reported. The apo structure of GCDH from Burkholderia pseudomallei reveals a loss of secondary structure and increased disorder in the FAD-binding pocket relative to the ternary complex of the highly homologous human GCDH. After conducting a fragment-based screen, four small molecules were identified which bind to GCDH from B. pseudomallei. Complex structures were determined for these fragments, which cause backbone and side-chain perturbations to key active-site residues. Structural insights from this investigation highlight differences from apo GCDH and the utility of small-molecular fragments as chemical probes for capturing alternative conformational states of preformed protein crystals.


  • Organizational Affiliation

    Seattle Structural Genomics Center for Infectious Disease (http://www.ssgcid.org), USA. dbegley@embios.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Glutaryl-CoA dehydrogenase
A, B, C, D
399Burkholderia pseudomallei 1710bMutation(s): 0 
Gene Names: BURPS1710b_3237
EC: 1.3.99.7
UniProt
Find proteins for Q3JP94 (Burkholderia pseudomallei (strain 1710b))
Explore Q3JP94 
Go to UniProtKB:  Q3JP94
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ3JP94
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.99 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.202 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 97.418α = 90
b = 106.374β = 90
c = 144.774γ = 90
Software Package:
Software NamePurpose
ADSCdata collection
MOLREPphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-04-28
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Source and taxonomy, Version format compliance
  • Version 1.2: 2011-09-21
    Changes: Database references
  • Version 1.3: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description