1XRT

The Crystal Structure of a Novel, Latent Dihydroorotase from Aquifex Aeolicus at 1.7 A Resolution


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.61 Å
  • R-Value Free: 0.208 
  • R-Value Work: 0.165 
  • R-Value Observed: 0.167 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

The crystal structure of a novel, latent dihydroorotase from Aquifex aeolicus at 1.7A resolution

Martin, P.D.Purcarea, C.Zhang, P.Vaishnav, A.Sadecki, S.Guy-Evans, H.I.Evans, D.R.Edwards, B.F.

(2005) J Mol Biol 348: 535-547

  • DOI: https://doi.org/10.1016/j.jmb.2005.03.015
  • Primary Citation of Related Structures:  
    1XRF, 1XRT

  • PubMed Abstract: 

    Dihydroorotases (EC 3.5.2.3) catalyze the reversible cyclization of carbamoyl aspartate to form dihydroorotate in de novo pyrimidine biosynthesis. The X-ray structures of Aquifex aeolicus dihydroorotase in two space groups, C222(1) and C2, were determined at a resolution of 1.7A. These are the first structures of a type I dihydroorotase, a class of molecules that includes the dihydroorotase domain of mammalian CAD. The type I enzymes are more ancient and larger, at 45 kDa, than the type II enzymes exemplified by the 38 kDa Escherichia coli dihydroorotase. Both dihydroorotases are members of the metallo-dependent hydrolase superfamily, whose members have a distorted "TIM barrel" domain containing the active site. However, A.aeolicus dihydroorotase has a second, composite domain, which the E.coli enzyme lacks and has only one of the two zinc atoms present in the E.coli enzyme. A.aeolicus dihydroorotase is unique in exhibiting significant activity only when complexed with aspartate transcarbamoylase, whereas the E.coli dihydroorotase and the CAD dihydroorotase domain are active as free proteins. The latency of A.aeolicus dihydroorotase can be related to two differences between its structure and that of E.coli dihydroorotase: (1) the monoclinic structure has a novel cysteine ligand to the zinc that blocks the active site and possibly functions as a "cysteine switch"; and (2) active site residues that bind the substrate in E.coli dihydroorotase are located in disordered loops in both crystal structures of A.aeolicus dihydroorotase and may function as a disorder-to-order "entropy switch".


  • Organizational Affiliation

    Wayne State University School of Medicine, Department of Biochemistry and Molecular Biology, 540 E. Canfield, Detroit, MI 48201, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Dihydroorotase
A, B
467Aquifex aeolicusMutation(s): 0 
Gene Names: pyrC
EC: 3.5.2.3
UniProt
Find proteins for O66990 (Aquifex aeolicus (strain VF5))
Explore O66990 
Go to UniProtKB:  O66990
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO66990
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.61 Å
  • R-Value Free: 0.208 
  • R-Value Work: 0.165 
  • R-Value Observed: 0.167 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 174.201α = 90
b = 91.235β = 93.15
c = 61.183γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
CrystalCleardata reduction
d*TREKdata scaling
CCP4phasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-07-05
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.3: 2023-08-23
    Changes: Data collection, Database references, Derived calculations, Refinement description