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| | <StructureSection load='3nks' size='340' side='right'caption='[[3nks]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='3nks' size='340' side='right'caption='[[3nks]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3nks]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NKS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NKS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3nks]] 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=3NKS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NKS FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACJ:5-[2-CHLORO-4-(TRIFLUOROMETHYL)PHENOXY]-2-NITROBENZOIC+ACID'>ACJ</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 1.9Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3i6d|3i6d]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACJ:5-[2-CHLORO-4-(TRIFLUOROMETHYL)PHENOXY]-2-NITROBENZOIC+ACID'>ACJ</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPOX ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Protoporphyrinogen_oxidase Protoporphyrinogen oxidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.3.4 1.3.3.4] </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=3nks FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nks OCA], [https://pdbe.org/3nks PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nks RCSB], [https://www.ebi.ac.uk/pdbsum/3nks PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nks ProSAT]</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=3nks FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nks OCA], [https://pdbe.org/3nks PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nks RCSB], [https://www.ebi.ac.uk/pdbsum/3nks PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nks ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/PPOX_HUMAN PPOX_HUMAN]] Porphyria variegata. Defects in PPOX are the cause of variegate porphyria (VP) [MIM:[https://omim.org/entry/176200 176200]]. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. PV is the most common form of porphyria in South Africa. It is characterized by skin hyperpigmentation and hypertrichosis, abdominal pain, tachycardia, hypertension and neuromuscular disturbances. High fecal levels of protoporphyrin and coproporphyrin, increased urine uroporphyrins and iron overload are typical markers of the disease.<ref>PMID:8852667</ref> <ref>PMID:8673113</ref> <ref>PMID:9763307</ref>
| + | [https://www.uniprot.org/uniprot/PPOX_HUMAN PPOX_HUMAN] Porphyria variegata. Defects in PPOX are the cause of variegate porphyria (VP) [MIM:[https://omim.org/entry/176200 176200]. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. PV is the most common form of porphyria in South Africa. It is characterized by skin hyperpigmentation and hypertrichosis, abdominal pain, tachycardia, hypertension and neuromuscular disturbances. High fecal levels of protoporphyrin and coproporphyrin, increased urine uroporphyrins and iron overload are typical markers of the disease.<ref>PMID:8852667</ref> <ref>PMID:8673113</ref> <ref>PMID:9763307</ref> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/PPOX_HUMAN PPOX_HUMAN]] Catalyzes the 6-electron oxidation of protoporphyrinogen-IX to form protoporphyrin-IX.
| + | [https://www.uniprot.org/uniprot/PPOX_HUMAN PPOX_HUMAN] Catalyzes the 6-electron oxidation of protoporphyrinogen-IX to form protoporphyrin-IX. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Protoporphyrinogen oxidase]]
| + | [[Category: Shen Y]] |
| - | [[Category: Shen, Y]] | + | |
| - | [[Category: Fad containing protein]]
| + | |
| - | [[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
| + | |
| - | [[Category: Ppo]]
| + | |
| - | [[Category: Variegate porphyria disease]]
| + | |
| - | [[Category: Vp]]
| + | |
| Structural highlights
Disease
PPOX_HUMAN Porphyria variegata. Defects in PPOX are the cause of variegate porphyria (VP) [MIM:176200. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. PV is the most common form of porphyria in South Africa. It is characterized by skin hyperpigmentation and hypertrichosis, abdominal pain, tachycardia, hypertension and neuromuscular disturbances. High fecal levels of protoporphyrin and coproporphyrin, increased urine uroporphyrins and iron overload are typical markers of the disease.[1] [2] [3]
Function
PPOX_HUMAN Catalyzes the 6-electron oxidation of protoporphyrinogen-IX to form protoporphyrin-IX.
Publication Abstract from PubMed
Human protoporphyrinogen IX oxidase (hPPO), a mitochondrial inner membrane protein, converts protoporphyrinogen IX to protoporphyrin IX in the heme biosynthetic pathway. Mutations in the hPPO gene cause the inherited human disease variegate porphyria (VP). In this study, we report the crystal structure of hPPO in complex with the coenzyme flavin adenine dinucleotide (FAD) and the inhibitor acifluorfen at a resolution of 1.9 A. The structural and biochemical analyses revealed the molecular details of FAD and acifluorfen binding to hPPO as well as the interactions of the substrate with hPPO. Structural analysis and gel chromatography indicated that hPPO is a monomer rather than a homodimer in vitro. The founder-effect mutation R59W in VP patients is most likely caused by a severe electrostatic hindrance in the hydrophilic binding pocket involving the bulky, hydrophobic indolyl ring of the tryptophan. Forty-seven VP-causing mutations were purified by chromatography and kinetically characterized in vitro. The effect of each mutation was demonstrated in the high-resolution crystal structure.
Structural insight into human variegate porphyria disease.,Qin X, Tan Y, Wang L, Wang Z, Wang B, Wen X, Yang G, Xi Z, Shen Y FASEB J. 2011 Feb;25(2):653-64. Epub 2010 Nov 3. PMID:21048046[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Deybach JC, Puy H, Robreau AM, Lamoril J, Da Silva V, Grandchamp B, Nordmann Y. Mutations in the protoporphyrinogen oxidase gene in patients with variegate porphyria. Hum Mol Genet. 1996 Mar;5(3):407-10. PMID:8852667
- ↑ Meissner PN, Dailey TA, Hift RJ, Ziman M, Corrigall AV, Roberts AG, Meissner DM, Kirsch RE, Dailey HA. A R59W mutation in human protoporphyrinogen oxidase results in decreased enzyme activity and is prevalent in South Africans with variegate porphyria. Nat Genet. 1996 May;13(1):95-7. PMID:8673113 doi:10.1038/ng0596-95
- ↑ Frank J, Poh-Fitzpatrick MB, King LE Jr, Christiano AM. The genetic basis of "Scarsdale Gourmet Diet" variegate porphyria: a missense mutation in the protoporphyrinogen oxidase gene. Arch Dermatol Res. 1998 Aug;290(8):441-5. PMID:9763307
- ↑ Qin X, Tan Y, Wang L, Wang Z, Wang B, Wen X, Yang G, Xi Z, Shen Y. Structural insight into human variegate porphyria disease. FASEB J. 2011 Feb;25(2):653-64. Epub 2010 Nov 3. PMID:21048046 doi:10.1096/fj.10-170811
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