2aex: Difference between revisions

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 ==The 1.58A Crystal Structure of Human Coproporphyrinogen Oxidase Reveals the Structural Basis of Hereditary Coproporphyria==
-<StructureSection load='2aex' size='340' side='right' caption='[[2aex]], [[Resolution|resolution]] 1.58&Aring;' scene=''>
+<StructureSection load='2aex' size='340' side='right'caption='[[2aex]], [[Resolution|resolution]] 1.58&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2aex]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AEX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AEX FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2aex]] 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=2AEX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AEX FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.58&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CPOX, CPO, CPX ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Coproporphyrinogen_oxidase Coproporphyrinogen oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.3.3 1.3.3.3] </span></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=2aex FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aex OCA], [https://pdbe.org/2aex PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2aex RCSB], [https://www.ebi.ac.uk/pdbsum/2aex PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2aex ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2aex FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aex OCA], [http://pdbe.org/2aex PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2aex RCSB], [http://www.ebi.ac.uk/pdbsum/2aex PDBsum]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/HEM6_HUMAN HEM6_HUMAN]] Defects in CPOX are the cause of hereditary coproporphyria (HCP) [MIM:[http://omim.org/entry/121300 121300]]. HCP is an acute hepatic porphyria and an autosomal dominant disease characterized by neuropsychiatric disturbances and skin photosensitivity. Biochemically, there is an overexcretion of coproporphyrin III in the urine and in the feces. HCP is clinically characterized by attacks of abdominal pain, neurological disturbances, and psychiatric symptoms. The symptoms are generally manifested with rapid onset, and can be precipitated by drugs, alcohol, caloric deprivation, infection, endocrine factors or stress. A severe variant form is harderoporphyria, which is characterized by earlier onset attacks, massive excretion of harderoporphyrin in the feces, and a marked decrease of coproporphyrinogen IX oxidase activity.<ref>PMID:8012360</ref> <ref>PMID:7849704</ref> <ref>PMID:7757079</ref> <ref>PMID:9048920</ref> <ref>PMID:8990017</ref> <ref>PMID:9298818</ref> <ref>PMID:9888388</ref> <ref>PMID:12181641</ref> <ref>PMID:15896662</ref> <ref>PMID:16398658</ref>
+[https://www.uniprot.org/uniprot/HEM6_HUMAN HEM6_HUMAN] Defects in CPOX are the cause of hereditary coproporphyria (HCP) [MIM:[https://omim.org/entry/121300 121300]. HCP is an acute hepatic porphyria and an autosomal dominant disease characterized by neuropsychiatric disturbances and skin photosensitivity. Biochemically, there is an overexcretion of coproporphyrin III in the urine and in the feces. HCP is clinically characterized by attacks of abdominal pain, neurological disturbances, and psychiatric symptoms. The symptoms are generally manifested with rapid onset, and can be precipitated by drugs, alcohol, caloric deprivation, infection, endocrine factors or stress. A severe variant form is harderoporphyria, which is characterized by earlier onset attacks, massive excretion of harderoporphyrin in the feces, and a marked decrease of coproporphyrinogen IX oxidase activity.<ref>PMID:8012360</ref> <ref>PMID:7849704</ref> <ref>PMID:7757079</ref> <ref>PMID:9048920</ref> <ref>PMID:8990017</ref> <ref>PMID:9298818</ref> <ref>PMID:9888388</ref> <ref>PMID:12181641</ref> <ref>PMID:15896662</ref> <ref>PMID:16398658</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/HEM6_HUMAN HEM6_HUMAN]] Key enzyme in heme biosynthesis. Catalyzes the oxidative decarboxylation of propionic acid side chains of rings A and B of coproporphyrinogen III.
+[https://www.uniprot.org/uniprot/HEM6_HUMAN HEM6_HUMAN] Key enzyme in heme biosynthesis. Catalyzes the oxidative decarboxylation of propionic acid side chains of rings A and B of 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/ae/2aex_consurf.spt"</scriptWhenChecked>
+     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ae/2aex_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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=2aex ConSurf].
 <div style="clear:both"></div>
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-Hereditary coproporphyria is an autosomal dominant disorder resulting from the half-normal activity of coproporphyrinogen oxidase (CPO), a mitochondrial enzyme catalyzing the antepenultimate step in heme biosynthesis. The mechanism by which CPO catalyzes oxidative decarboxylation, in an extraordinary metal- and cofactor-independent manner, is poorly understood. Here, we report the crystal structure of human CPO at 1.58-A resolution. The structure reveals a previously uncharacterized tertiary topology comprising an unusually flat seven-stranded beta-sheet sandwiched by alpha-helices. In the biologically active dimer (K(D) = 5 x 10(-7) M), one monomer rotates relative to the second by approximately 40 degrees to create an intersubunit interface in close proximity to two independent enzymatic sites. The unexpected finding of citrate at the active site allows us to assign Ser-244, His-258, Asn-260, Arg-262, Asp-282, and Arg-332 as residues mediating substrate recognition and decarboxylation. We favor a mechanism in which oxygen serves as the immediate electron acceptor, and a substrate radical or a carbanion with substantial radical character participates in catalysis. Although several mutations in the CPO gene have been described, the molecular basis for how these alterations diminish enzyme activity is unknown. We show that deletion of residues (392-418) encoded by exon six disrupts dimerization. Conversely, harderoporphyria-causing K404E mutation precludes a type I beta-turn from retaining the substrate for the second decarboxylation cycle. Together, these findings resolve several questions regarding CPO catalysis and provide insights into hereditary coproporphyria.
-Structural basis of hereditary coproporphyria.,Lee DS, Flachsova E, Bodnarova M, Demeler B, Martasek P, Raman CS Proc Natl Acad Sci U S A. 2005 Oct 4;102(40):14232-7. Epub 2005 Sep 21. PMID:16176984<ref>PMID:16176984</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 2aex" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Coproporphyrinogen oxidase]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
+[[Category: Large Structures]]
-[[Category: Bodnarova, M]]
+[[Category: Bodnarova M]]
-[[Category: Demeler, B]]
+[[Category: Demeler B]]
-[[Category: Flachsova, E]]
+[[Category: Flachsova E]]
-[[Category: Lee, D S]]
+[[Category: Lee DS]]
-[[Category: Martasek, P]]
+[[Category: Martasek P]]
-[[Category: Raman, C S]]
+[[Category: Raman CS]]
-[[Category: Flat beta-sheet sandwiched by helice]]
-[[Category: Oxidoreductase]]