2q6z
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Hepatoerythropoietic porphyria (HEP) is a rare form of porphyria in | + | 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. |
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| + | ==Disease== | ||
| + | Known diseases associated with this structure: Porphyria cutanea tarda OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176100 176100]], Porphyria, hepatoerythropoietic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176100 176100]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Uroporphyrinogen decarboxylase]] | [[Category: Uroporphyrinogen decarboxylase]] | ||
| - | [[Category: Edwards, C | + | [[Category: Edwards, C Q.]] |
| - | [[Category: Hill, C | + | [[Category: Hill, C P.]] |
| - | [[Category: Kushner, J | + | [[Category: Kushner, J P.]] |
| - | [[Category: Phillips, J | + | [[Category: Phillips, J D.]] |
| - | [[Category: Stadtmueller, B | + | [[Category: Stadtmueller, B M.]] |
| - | [[Category: Whitby, F | + | [[Category: Whitby, F G.]] |
[[Category: uroporphyrinogen decarboxylase enzyme urod g168r coproporphyrinogen]] | [[Category: uroporphyrinogen decarboxylase enzyme urod g168r coproporphyrinogen]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:36:40 2008'' |
Revision as of 16:36, 21 February 2008
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Uroporphyrinogen Decarboxylase G168R single mutant apo-enzyme
Contents |
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.
Disease
Known diseases associated with this structure: Porphyria cutanea tarda OMIM:[176100], Porphyria, hepatoerythropoietic OMIM:[176100]
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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