3WK2

Orotidine 5'-monophosphate decarboxylase K72A mutant from M. thermoautotrophicus complexed with orotidine 5'-monophosphate methyl ester


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.69 Å
  • R-Value Free: 0.183 
  • R-Value Work: 0.164 
  • R-Value Observed: 0.165 

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This is version 1.1 of the entry. See complete history


Literature

Substrate distortion contributes to the catalysis of orotidine 5'-monophosphate decarboxylase.

Fujihashi, M.Ishida, T.Kuroda, S.Kotra, L.P.Pai, E.F.Miki, K.

(2013) J Am Chem Soc 135: 17432-17443

  • DOI: https://doi.org/10.1021/ja408197k
  • Primary Citation of Related Structures:  
    3WJW, 3WJX, 3WJY, 3WJZ, 3WK0, 3WK1, 3WK2, 3WK3

  • PubMed Abstract: 

    Orotidine 5'-monophosphate decarboxylase (ODCase) accelerates the decarboxylation of orotidine 5'-monophosphate (OMP) to uridine 5'-monophosphate (UMP) by 17 orders of magnitude. Eight new crystal structures with ligand analogues combined with computational analyses of the enzyme's short-lived intermediates and the intrinsic electronic energies to distort the substrate and other ligands improve our understanding of the still controversially discussed reaction mechanism. In their respective complexes, 6-methyl-UMP displays significant distortion of its methyl substituent bond, 6-amino-UMP shows the competition between the K72 and C6 substituents for a position close to D70, and the methyl and ethyl esters of OMP both induce rotation of the carboxylate group substituent out of the plane of the pyrimidine ring. Molecular dynamics and quantum mechanics/molecular mechanics computations of the enzyme-substrate complex also show the bond between the carboxylate group and the pyrimidine ring to be distorted, with the distortion contributing a 10-15% decrease of the ΔΔG(⧧) value. These results are consistent with ODCase using both substrate distortion and transition-state stabilization, primarily exerted by K72, in its catalysis of the OMP decarboxylation reaction.


  • Organizational Affiliation

    Department of Chemistry, Graduate School of Science, Kyoto University , Sakyo-ku, Kyoto 606-8502, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Orotidine 5'-phosphate decarboxylase252Methanothermobacter thermautotrophicusMutation(s): 3 
Gene Names: pyrFMTH_129
EC: 4.1.1.23
UniProt
Find proteins for O26232 (Methanothermobacter thermautotrophicus (strain ATCC 29096 / DSM 1053 / JCM 10044 / NBRC 100330 / Delta H))
Explore O26232 
Go to UniProtKB:  O26232
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO26232
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.69 Å
  • R-Value Free: 0.183 
  • R-Value Work: 0.164 
  • R-Value Observed: 0.165 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 57.833α = 90
b = 103.388β = 90
c = 73.27γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
PDB_EXTRACTdata extraction
HKL-2000data collection
HKL-2000data reduction
HKL-2000data scaling
REFMACphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-12-04
    Type: Initial release
  • Version 1.1: 2023-11-08
    Changes: Data collection, Database references, Derived calculations, Refinement description