2q6z
From Proteopedia
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Uroporphyrinogen Decarboxylase G168R single mutant apo-enzyme
Overview
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.
About this Structure
2Q6Z is a Single protein structure of sequence from Homo sapiens. Active as Uroporphyrinogen decarboxylase, with EC number 4.1.1.37 Full crystallographic information is available from OCA.
Reference
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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