2q71
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| , resolution 1.900Å | |||||||
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| Ligands: | |||||||
| Gene: | UROD (Homo sapiens) | ||||||
| Activity: | Uroporphyrinogen decarboxylase, with EC number 4.1.1.37 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Uroporphyrinogen Decarboxylase G168R single mutant enzyme in complex with coproporphyrinogen-III
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Porphyria cutanea tarda OMIM:[176100], Porphyria, hepatoerythropoietic OMIM:[176100]
About this StructureAbout this Structure
2Q71 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Two novel uroporphyrinogen decarboxylase (URO-D) mutations causing hepatoerythropoietic porphyria (HEP)., Phillips JD, Whitby FG, Stadtmueller BM, Edwards CQ, Hill CP, Kushner JP, Transl Res. 2007 Feb;149(2):85-91. PMID:17240319
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