1JPK

Gly156Asp mutant of Human UroD, human uroporphyrinogen III decarboxylase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.195 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Functional consequences of naturally occurring mutations in human uroporphyrinogen decarboxylase.

Phillips, J.D.Parker, T.L.Schubert, H.L.Whitby, F.G.Hill, C.P.Kushner, J.P.

(2001) Blood 98: 3179-3185

  • DOI: https://doi.org/10.1182/blood.v98.12.3179
  • Primary Citation of Related Structures:  
    1JPH, 1JPI, 1JPK

  • PubMed Abstract: 

    Functional consequences of 12 mutations-10 missense, 1 splicing defect, and 1 frameshift mutation-were characterized in the uroporphyrinogen decarboxylase (URO-D) gene found in Utah pedigrees with familial porphyria cutanea tarda (F-PCT). All but one mutation altered a restriction site in the URO-D gene, permitting identification of affected relatives using a combination of polymerase chain reaction and restriction enzyme digestion. In a bacterial expression system, 3 of the missense mutants were found in inclusion bodies, but 7 were expressed as soluble proteins. Enzymatic activity of soluble, recombinant mutant URO-D genes ranged from 29% to 94% of normal. URO-D mRNA levels in Epstein-Barr-virus transformed cells derived from patients were normal (with the exception of the frameshift mutation) even though protein levels were lower than normal, suggesting that missense mutations generally cause unstable URO-Ds in vivo. The crystal structures of 3 mutant URO-Ds were solved, and the structural consequences of the mutations were defined. All missense mutations reported here and by others were mapped to the crystal structure of URO-D, and structural effects were predicted. These studies define structural and functional consequences of URO-D mutations occurring in patients with F-PCT.


  • Organizational Affiliation

    Department of Medicine, University of Utah School of Medicine, Salt Lake City 84132, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
UROPORPHYRINOGEN DECARBOXYLASE388Homo sapiensMutation(s): 1 
Gene Names: UroD
EC: 4.1.1.37
UniProt & NIH Common Fund Data Resources
Find proteins for P06132 (Homo sapiens)
Explore P06132 
Go to UniProtKB:  P06132
PHAROS:  P06132
GTEx:  ENSG00000126088 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP06132
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.195 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 103.2α = 90
b = 103.2β = 90
c = 73.62γ = 120
Software Package:
Software NamePurpose
X-PLORmodel building
X-PLORrefinement
DENZOdata reduction
SCALEPACKdata scaling
X-PLORphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2001-12-19
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2021-10-27
    Changes: Database references
  • Version 1.4: 2023-08-16
    Changes: Data collection, Refinement description