2q71
From Proteopedia
(New page: 200px<br /> <applet load="2q71" size="450" color="white" frame="true" align="right" spinBox="true" caption="2q71, resolution 1.900Å" /> '''Uroporphyrinogen D...) |
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| - | [[Image:2q71. | + | [[Image:2q71.jpg|left|200px]]<br /><applet load="2q71" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2q71" size=" | + | |
caption="2q71, resolution 1.900Å" /> | caption="2q71, resolution 1.900Å" /> | ||
'''Uroporphyrinogen Decarboxylase G168R single mutant enzyme in complex with coproporphyrinogen-III'''<br /> | '''Uroporphyrinogen Decarboxylase G168R single mutant enzyme in complex with coproporphyrinogen-III'''<br /> | ||
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==Overview== | ==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. | 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== | ||
| - | 2Q71 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CP3 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Uroporphyrinogen_decarboxylase Uroporphyrinogen decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.37 4.1.1.37] Full crystallographic information is available from [http:// | + | 2Q71 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CP3:'>CP3</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Uroporphyrinogen_decarboxylase Uroporphyrinogen decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.37 4.1.1.37] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q71 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: uroporphyrinogen decarboxylase enzyme urod g168r coproporphyrinogen-iii product complex]] | [[Category: uroporphyrinogen decarboxylase enzyme urod g168r coproporphyrinogen-iii product complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:51:22 2008'' |
Revision as of 12:51, 23 January 2008
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Uroporphyrinogen Decarboxylase G168R single mutant enzyme in complex with coproporphyrinogen-III
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
2Q71 is a Single protein structure of sequence from Homo sapiens with as ligand. 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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