PDBsum entry: 2q71

Lyase

PDB id: 2q71

Contents

Protein chain

356 a.a. *

Ligands

CP3

Waters ×383

* Residue conservation analysis

PDB id:

2q71

Name:

Lyase

Title:

Uroporphyrinogen decarboxylase g168r single mutant enzyme in complex with coproporphyrinogen-iii

Structure:

Uroporphyrinogen decarboxylase. Chain: a. Synonym: uro-d, upd. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: urod. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.90Å R-factor: 0.164 R-free: 0.199

Authors:

J.D.Phillips,F.G.Whitby,B.M.Stadtmueller,C.Q.Edwards, C.P.Hill,J.P.Kushner

Key ref:

J.D.Phillips et al. (2007). Two novel uroporphyrinogen decarboxylase (URO-D) mutations causing hepatoerythropoietic porphyria (HEP). Transl Res, 149, 85-91. PubMed id: 17240319 DOI: 10.1016/j.trsl.2006.08.006

Date:

05-Jun-07 Release date: 19-Jun-07

Protein chain

P06132  (DCUP_HUMAN) -  Uroporphyrinogen decarboxylase

Seq: 367 a.a.

Struc: 356 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.4.1.1.37 - Uroporphyrinogen decarboxylase.
• Pathway: Porphyrin Biosynthesis (later stages)
• Reaction: Uroporphyrinogen III = coproporphyrinogen + 4 CO₂

Uroporphyrinogen III (Bound ligand (Het Group name = CP3) matches with 80.00% similarity) = coproporphyrinogen + 4 × CO(2)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Cellular component: cytoplasm (5 terms)
• Biological process: metabolic process (16 terms)
• Biochemical function: lyase activity (4 terms)

Added reference

DOI no: 10.1016/j.trsl.2006.08.006

Transl Res 149:85-91 (2007)

PubMed id: 17240319

Two novel uroporphyrinogen decarboxylase (URO-D) mutations causing hepatoerythropoietic porphyria (HEP).

J.D.Phillips, F.G.Whitby, B.M.Stadtmueller, C.Q.Edwards, C.P.Hill, J.P.Kushner.

ABSTRACT

Hepatoerythropoietic porphyria (HEP) is a rare form of porphyria in humans. The disorder is caused by homozygosity or compound heterozygosity for mutations of the uroporphyrinogen decarboxylase (URO-D) gene. Subnormal URO-D activity results in accumulation of uroporphyrin in the liver, which ultimately mediates the photosensitivity that clinically characterizes HEP. Two previously undescribed URO-D mutations found in a 2-year-old Caucasian boy with HEP, a maternal nonsense mutation (Gln71Stop), and a paternal missense mutation (Gly168Arg) are reported here. Recombinant Gly168Arg URO-D retained 65% of wild-type URO-D activity and studies in Epstein-Barr Virus (EBV)-transformed lymphoblasts indicated that protein levels are reduced, suggesting that the mutant protein might be subjected to accelerated turnover. The crystal structure of Gly168Arg was determined both as the apo-enzyme and with the reaction product bound. These studies revealed little distortion of the active site, but a loop containing residues 167-172 was displaced, possibly indicating small changes in the catalytic geometry or in substrate binding or increased accessibility to a cellular proteolytic pathway. A second pregnancy occurred in this family, and in utero genotyping revealed a fetus heterozygous for the maternal nonsense mutation (URO-D genotype WT/Gln71Stop). A healthy infant was born with no clinical evidence of porphyria.