1NR1

Crystal structure of the R463A mutant of human Glutamate dehydrogenase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.30 Å
  • R-Value Free: 0.284 
  • R-Value Work: 0.222 
  • R-Value Observed: 0.222 

wwPDB Validation   3D Report Full Report


This is version 1.6 of the entry. See complete history


Literature

Structural studies on ADP activation of mammalian glutamate dehydrogenase and the evolution of regulation

Banerjee, S.Schmidt, T.Fang, J.Stanley, C.A.Smith, T.J.

(2003) Biochemistry 42: 3446-3456

  • DOI: https://doi.org/10.1021/bi0206917
  • Primary Citation of Related Structures:  
    1NQT, 1NR1, 1NR7, 6DHK

  • PubMed Abstract: 

    Glutamate dehydrogenase (GDH) is found in all organisms and catalyzes the reversible oxidative deamination of L-glutamate to 2-oxoglutarate. Unlike GDH from bacteria, mammalian GDH exhibits negative cooperativity with respect to coenzyme, activation by ADP, and inhibition by GTP. Presented here are the structures of apo bovine GDH, bovine GDH complexed with ADP, and the R463A mutant form of human GDH (huGDH) that is insensitive to ADP activation. In the absence of active site ligands, the catalytic cleft is in the open conformation, and the hexamers form long polymers in the crystal cell with more interactions than found in the abortive complex crystals. This is consistent with the fact that ADP promotes aggregation in solution. ADP is shown to bind to the second, inhibitory, NADH site yet causes activation. The beta-phosphates of the bound ADP interact with R459 (R463 in huGDH) on the pivot helix. The structure of the ADP-resistant, R463A mutant of human GDH is identical to native GDH with the exception of the truncated side chain on the pivot helix. Together, these results strongly suggest that ADP activates by facilitating the opening of the catalytic cleft. From alignment of GDH from various sources, it is likely that the antenna evolved in the protista prior to the formation of purine regulatory sites. This suggests that there was some selective advantage of the antenna itself and that animals evolved new functions for GDH through the addition of allosteric regulation.


  • Organizational Affiliation

    Donald Danforth Plant Science Center, St. Louis, Missouri 63132, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Glutamate dehydrogenase 1
A, B, C, D, E
A, B, C, D, E, F
496Homo sapiensMutation(s): 1 
EC: 1.4.1.3
UniProt & NIH Common Fund Data Resources
Find proteins for P00367 (Homo sapiens)
Explore P00367 
Go to UniProtKB:  P00367
PHAROS:  P00367
GTEx:  ENSG00000148672 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00367
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.30 Å
  • R-Value Free: 0.284 
  • R-Value Work: 0.222 
  • R-Value Observed: 0.222 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 96.92α = 86.48
b = 98.64β = 69.69
c = 124.26γ = 60.87
Software Package:
Software NamePurpose
SCALEPACKdata scaling
CNSrefinement
CNSphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2003-05-06
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-02-08
    Changes: Structure summary
  • Version 1.4: 2017-10-11
    Changes: Refinement description
  • Version 1.5: 2021-10-27
    Changes: Database references
  • Version 1.6: 2024-02-14
    Changes: Data collection