View source for 2q71

[[Image:2q71.gif|left|200px]]<br />
<applet load="2q71" size="450" color="white" frame="true" align="right" spinBox="true" 
caption="2q71, resolution 1.900&Aring;" />
'''Uroporphyrinogen Decarboxylase G168R single mutant enzyme in complex with coproporphyrinogen-III'''<br />

==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:[[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==
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://ispc.weizmann.ac.il/oca-bin/ocashort?id=2Q71 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17240319 17240319]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Uroporphyrinogen decarboxylase]]
[[Category: Edwards, C.Q.]]
[[Category: Hill, C.P.]]
[[Category: Kushner, J.P.]]
[[Category: Phillips, J.D.]]
[[Category: Stadtmueller, B.M.]]
[[Category: Whitby, F.G.]]
[[Category: CP3]]
[[Category: uroporphyrinogen decarboxylase enzyme urod g168r coproporphyrinogen-iii product complex]]

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