1AS0

GTP-GAMMA-S BOUND G42V GIA1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.206 

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This is version 1.4 of the entry. See complete history


Literature

Structural and biochemical characterization of the GTPgammaS-, GDP.Pi-, and GDP-bound forms of a GTPase-deficient Gly42 --> Val mutant of Gialpha1.

Raw, A.S.Coleman, D.E.Gilman, A.G.Sprang, S.R.

(1997) Biochemistry 36: 15660-15669

  • DOI: https://doi.org/10.1021/bi971912p
  • Primary Citation of Related Structures:  
    1AS0, 1AS2, 1AS3

  • PubMed Abstract: 

    The Gly42 --> Val mutant of Gialpha1 was characterized structurally and biochemically to elucidate two important features of Gialpha1-catalyzed GTP hydrolysis. The crystal structure of the GTPgammaS-bound G42VGialpha1 protein demonstrates that the steric bulk of Val42 pushes the Gln204 residue into a catalytically incompetent conformation, providing a rationale for the diminished GTPase activity of this mutant. The same phenomenon may also account for the diminished GTPase activity of the homologous transforming Gly42 --> Val mutation in p21(ras). Similarly, the steric bulk of the unique Ser42 residue in Gzalpha may account for the comparatively slower rate of GTP hydrolysis by this Galpha subunit. The G42VGialpha1 subunit was also characterized structurally in its GDP.Pi- and GDP-bound states, providing a unique opportunity to view three "snapshots" of GTP hydrolysis. Hydrolysis of GTP to a transient GDP.Pi-bound intermediate is associated with substantial conformational changes in the switch II segment of the protein. Eventual release of Pi results in further removal of switch I from the active site and a highly mobile switch II segment. Despite their disparate biochemical properties, the structural similarity of G42VGialpha1 to the G203AGialpha1 mutant in the GDP.Pi-bound form suggests that both mutations stabilize a conformation of the GDP. Pi-bound protein that occurs only transiently in the wild-type protein. The structures of the GDP-bound forms of the wild-type and mutant proteins are similar.


  • Organizational Affiliation

    Department of Pharmacology, and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
GIA1353Rattus norvegicusMutation(s): 1 
UniProt
Find proteins for P10824 (Rattus norvegicus)
Explore P10824 
Go to UniProtKB:  P10824
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP10824
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.206 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 78.95α = 90
b = 78.95β = 90
c = 105.29γ = 120
Software Package:
Software NamePurpose
X-PLORmodel building
X-PLORrefinement
DENZOdata reduction
SCALEPACKdata scaling
X-PLORphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1997-11-12
    Type: Initial release
  • Version 1.1: 2008-03-24
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2021-11-03
    Changes: Database references, Derived calculations, Other
  • Version 1.4: 2023-08-02
    Changes: Refinement description