1R6U

Crystal structure of an active fragment of human tryptophanyl-tRNA synthetase with cytokine activity


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.297 
  • R-Value Work: 0.254 
  • R-Value Observed: 0.255 

Starting Model: experimental
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This is version 1.4 of the entry. See complete history


Literature

Functional and crystal structure analysis of active site adaptations of a potent anti-angiogenic human tRNA synthetase

Yang, X.-L.Guo, M.Kapoor, M.Ewalt, K.L.Otero, F.J.Skene, R.J.McRee, D.E.Schimmel, P.

(2007) Structure 15: 793-805

  • DOI: https://doi.org/10.1016/j.str.2007.05.009
  • Primary Citation of Related Structures:  
    1R6U

  • PubMed Abstract: 

    Higher eukaryote tRNA synthetases have expanded functions that come from enlarged, more differentiated structures that were adapted to fit aminoacylation function. How those adaptations affect catalytic mechanisms is not known. Presented here is the structure of a catalytically active natural splice variant of human tryptophanyl-tRNA synthetase (TrpRS) that is a potent angiostatic factor. This and related structures suggest that a eukaryote-specific N-terminal extension of the core enzyme changed substrate recognition by forming an active site cap. At the junction of the extension and core catalytic unit, an arginine is recruited to replace a missing landmark lysine almost 200 residues away. Mutagenesis, rapid kinetic, and substrate binding studies support the functional significance of the cap and arginine recruitment. Thus, the enzyme function of human TrpRS has switched more to the N terminus of the sequence. This switch has the effect of creating selective pressure to retain the N-terminal extension for functional expansion.


  • Organizational Affiliation

    The Scripps Research Institute, BCC-379, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. [email protected]


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tryptophanyl-tRNA synthetase
A, B
437Homo sapiensMutation(s): 12 
Gene Names: WARS
EC: 6.1.1.2
UniProt & NIH Common Fund Data Resources
Find proteins for P23381 (Homo sapiens)
Explore P23381 
Go to UniProtKB:  P23381
PHAROS:  P23381
GTEx:  ENSG00000140105 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP23381
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.297 
  • R-Value Work: 0.254 
  • R-Value Observed: 0.255 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 134.658α = 90
b = 96.46β = 129.9
c = 97.132γ = 90
Software Package:
Software NamePurpose
Blu-Icedata collection
SCALEPACKdata scaling
SOLVEphasing
CNSrefinement

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-01-06
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2021-10-27
    Changes: Database references, Derived calculations
  • Version 1.4: 2024-10-30
    Changes: Data collection, Refinement description, Structure summary