2q6z
From Proteopedia
(New page: 200px<br /> <applet load="2q6z" size="450" color="white" frame="true" align="right" spinBox="true" caption="2q6z, resolution 2.000Å" /> '''Uroporphyrinogen D...) |
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| - | [[Image:2q6z.gif|left|200px]]<br /> | + | [[Image:2q6z.gif|left|200px]]<br /><applet load="2q6z" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="2q6z, resolution 2.000Å" /> | caption="2q6z, resolution 2.000Å" /> | ||
'''Uroporphyrinogen Decarboxylase G168R single mutant apo-enzyme'''<br /> | '''Uroporphyrinogen Decarboxylase G168R single mutant apo-enzyme'''<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== | ||
| - | 2Q6Z is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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:// | + | 2Q6Z is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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=2Q6Z OCA]. |
==Reference== | ==Reference== | ||
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[[Category: uroporphyrinogen decarboxylase enzyme urod g168r coproporphyrinogen]] | [[Category: uroporphyrinogen decarboxylase enzyme urod g168r coproporphyrinogen]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:45:40 2008'' |
Revision as of 12:45, 23 January 2008
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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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