2q71: Difference between revisions

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-[[Image:2q71.png|left|200px]]
-{{STRUCTURE_2q71|  PDB=2q71  |  SCENE=  }}
+==Uroporphyrinogen Decarboxylase G168R single mutant enzyme in complex with coproporphyrinogen-III==
+<StructureSection load='2q71' size='340' side='right'caption='[[2q71]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2q71]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q71 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q71 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CP3:COPROPORPHYRINOGEN+III'>CP3</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2q71 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q71 OCA], [https://pdbe.org/2q71 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q71 RCSB], [https://www.ebi.ac.uk/pdbsum/2q71 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q71 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/DCUP_HUMAN DCUP_HUMAN] Defects in UROD are the cause of familial porphyria cutanea tarda (FPCT) [MIM:[https://omim.org/entry/176100 176100]; also known as porphyria cutanea tarda type II. FPCT is an autosomal dominant disorder characterized by light-sensitive dermatitis, with onset in later life. It is associated with the excretion of large amounts of uroporphyrin in the urine. Iron overload is often present in association with varying degrees of liver damage. Besides the familial form of PCT, a relatively common idiosyncratic form is known in which only the liver enzyme is reduced. This form is referred to as porphyria cutanea tarda "sporadic" type or type I [MIM:[https://omim.org/entry/176090 176090]. PCT type I occurs sporadically as an unusual accompaniment of common hepatic disorders such as alcohol-associated liver disease.<ref>PMID:2243121</ref> <ref>PMID:11719352</ref> <ref>PMID:2920211</ref> <ref>PMID:7706766</ref> <ref>PMID:8896428</ref> <ref>PMID:9792863</ref> <ref>PMID:10338097</ref> <ref>PMID:10477430</ref> <ref>PMID:11069625</ref> <ref>PMID:11295834</ref>   Defects in UROD are the cause of hepatoerythropoietic porphyria (HEP) [MIM:[https://omim.org/entry/176100 176100]. HEP is a rare autosomal recessive disorder. It is the severe form of cutaneous porphyria, and presents in infancy. The level of UROD is very low in erythrocytes and cultured skin fibroblasts, suggesting that HEP is the homozygous state for porphyria cutanea tarda.<ref>PMID:8896428</ref> <ref>PMID:8644733</ref> <ref>PMID:3775362</ref> <ref>PMID:1905636</ref> <ref>PMID:1634232</ref> <ref>PMID:8176248</ref> <ref>PMID:12071824</ref> <ref>PMID:15491440</ref> <ref>PMID:17240319</ref> <ref>PMID:21668429</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/DCUP_HUMAN DCUP_HUMAN] Catalyzes the decarboxylation of four acetate groups of uroporphyrinogen-III to yield coproporphyrinogen-III.
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q7/2q71_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2q71 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+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.
-===Uroporphyrinogen Decarboxylase G168R single mutant enzyme in complex with coproporphyrinogen-III===
+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<ref>PMID:17240319</ref>
-{{ABSTRACT_PUBMED_17240319}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 2q71" style="background-color:#fffaf0;"></div>
-[[2q71]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q71 OCA].
+== References ==
+<references/>
-==Reference==
+__TOC__
-<ref group="xtra">PMID:017240319</ref><ref group="xtra">PMID:017591767</ref><references group="xtra"/>
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Uroporphyrinogen decarboxylase]]
+[[Category: Large Structures]]
-[[Category: Edwards, C Q.]]
+[[Category: Edwards CQ]]
-[[Category: Hill, C P.]]
+[[Category: Hill CP]]
-[[Category: Kushner, J P.]]
+[[Category: Kushner JP]]
-[[Category: Phillips, J D.]]
+[[Category: Phillips JD]]
-[[Category: Stadtmueller, B M.]]
+[[Category: Stadtmueller BM]]
-[[Category: Whitby, F G.]]
+[[Category: Whitby FG]]
-[[Category: Lyase]]
-[[Category: Uroporphyrinogen decarboxylase enzyme urod g168r coproporphyrinogen-iii product complex]]