2Q5I

Crystal structure of apo S581L Glycyl-tRNA synthetase mutant


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.249 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.214 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Crystal structure of human wildtype and S581L-mutant glycyl-tRNA synthetase, an enzyme underlying distal spinal muscular atrophy.

Cader, M.Z.Ren, J.James, P.A.Bird, L.E.Talbot, K.Stammers, D.K.

(2007) FEBS Lett 581: 2959-2964

  • DOI: https://doi.org/10.1016/j.febslet.2007.05.046
  • Primary Citation of Related Structures:  
    2Q5H, 2Q5I

  • PubMed Abstract: 

    Dominant mutations in the ubiquitous enzyme glycyl-tRNA synthetase (GlyRS), including S581L, lead to motor nerve degeneration. We have determined crystal structures of wildtype and S581L-mutant human GlyRS. The S581L mutation is approximately 50A from the active site, and yet gives reduced aminoacylation activity. The overall structures of wildtype and S581L-GlyRS, including the active site, are very similar. However, residues 567-575 of the anticodon-binding domain shift position and in turn could indirectly affect glycine binding via the tRNA or alternatively inhibit conformational changes. Reduced enzyme activity may underlie neuronal degeneration, although a dominant-negative effect is more likely in this autosomal dominant disorder.


  • Organizational Affiliation

    Henry Wellcome Building for Gene Function, MRC Functional Genetics Unit, University of Oxford, South Parks Road, Oxford OX1 3QX, United Kingdom.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Glycyl-tRNA synthetase691Homo sapiensMutation(s): 1 
Gene Names: GARS
EC: 6.1.1.14
UniProt & NIH Common Fund Data Resources
Find proteins for P41250 (Homo sapiens)
Explore P41250 
Go to UniProtKB:  P41250
PHAROS:  P41250
GTEx:  ENSG00000106105 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP41250
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.249 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.214 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 92.53α = 90
b = 92.53β = 90
c = 246.86γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data collection
DENZOdata reduction
SCALEPACKdata scaling
CNSphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-06-19
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Advisory, Derived calculations, Version format compliance
  • Version 1.3: 2021-10-20
    Changes: Database references, Derived calculations
  • Version 1.4: 2023-08-30
    Changes: Data collection, Refinement description