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| - | {{STRUCTURE_3qfc| PDB=3qfc | SCENE= }} | |
| - | ===Crystal Structure of Human NADPH-Cytochrome P450 (V492E mutant)=== | |
| - | {{ABSTRACT_PUBMED_21808038}} | |
| | | | |
| - | ==Disease== | + | ==Crystal Structure of Human NADPH-Cytochrome P450 (V492E mutant)== |
| - | [[http://www.uniprot.org/uniprot/NCPR_HUMAN NCPR_HUMAN]] Defects in POR are the cause of Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis (ABS1) [MIM:[http://omim.org/entry/201750 201750]]. A disease characterized by the association of Antley-Bixler syndrome with steroidogenesis defects and abnormal genitalia. Antley-Bixler syndrome is characterized by craniosynostosis, radiohumeral synostosis present from the perinatal period, midface hypoplasia, choanal stenosis or atresia, femoral bowing and multiple joint contractures.<ref>PMID:15264278</ref><ref>PMID:15483095</ref><ref>PMID:14758361</ref> Defects in POR are the cause of disordered steroidogenesis due to cytochrome P450 oxidoreductase deficiency (DISPORD) [MIM:[http://omim.org/entry/613571 613571]]. A disorder resulting in a rare variant of congenital adrenal hyperplasia, with apparent combined P450C17 and P450C21 deficiency and accumulation of steroid metabolites. Affected girls are born with ambiguous genitalia, but their circulating androgens are low and virilization does not progress. Conversely, affected boys are sometimes born undermasculinized. Boys and girls can present with bone malformations, in some cases resembling the pattern seen in patients with Antley-Bixler syndrome.<ref>PMID:14758361</ref><ref>PMID:15220035</ref> | + | <StructureSection load='3qfc' size='340' side='right'caption='[[3qfc]], [[Resolution|resolution]] 1.80Å' scene=''> |
| - | | + | == Structural highlights == |
| - | ==Function== | + | <table><tr><td colspan='2'>[[3qfc]] is a 2 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=3QFC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QFC FirstGlance]. <br> |
| - | [[http://www.uniprot.org/uniprot/NCPR_HUMAN NCPR_HUMAN]] This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5. | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> |
| - | | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> |
| - | ==About this Structure==
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3qfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qfc OCA], [https://pdbe.org/3qfc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qfc RCSB], [https://www.ebi.ac.uk/pdbsum/3qfc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qfc ProSAT]</span></td></tr> |
| - | [[3qfc]] is a 2 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=3QFC OCA].
| + | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/NCPR_HUMAN NCPR_HUMAN] Defects in POR are the cause of Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis (ABS1) [MIM:[https://omim.org/entry/201750 201750]. A disease characterized by the association of Antley-Bixler syndrome with steroidogenesis defects and abnormal genitalia. Antley-Bixler syndrome is characterized by craniosynostosis, radiohumeral synostosis present from the perinatal period, midface hypoplasia, choanal stenosis or atresia, femoral bowing and multiple joint contractures.<ref>PMID:15264278</ref> <ref>PMID:15483095</ref> <ref>PMID:14758361</ref> Defects in POR are the cause of disordered steroidogenesis due to cytochrome P450 oxidoreductase deficiency (DISPORD) [MIM:[https://omim.org/entry/613571 613571]. A disorder resulting in a rare variant of congenital adrenal hyperplasia, with apparent combined P450C17 and P450C21 deficiency and accumulation of steroid metabolites. Affected girls are born with ambiguous genitalia, but their circulating androgens are low and virilization does not progress. Conversely, affected boys are sometimes born undermasculinized. Boys and girls can present with bone malformations, in some cases resembling the pattern seen in patients with Antley-Bixler syndrome.<ref>PMID:14758361</ref> <ref>PMID:15220035</ref> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/NCPR_HUMAN NCPR_HUMAN] This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5. |
| | | | |
| | ==See Also== | | ==See Also== |
| | *[[NADPH-Cytochrome P450 Reductase|NADPH-Cytochrome P450 Reductase]] | | *[[NADPH-Cytochrome P450 Reductase|NADPH-Cytochrome P450 Reductase]] |
| - | | + | == References == |
| - | ==Reference== | + | <references/> |
| - | <ref group="xtra">PMID:021808038</ref><references group="xtra"/><references/>
| + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: NADPH--hemoprotein reductase]] | + | [[Category: Large Structures]] |
| - | [[Category: Kim, J J.P.]] | + | [[Category: Kim J-JP]] |
| - | [[Category: Marohnic, C.]] | + | [[Category: Marohnic C]] |
| - | [[Category: Masters, B S.]] | + | [[Category: Masters BS]] |
| - | [[Category: Panda, S P.]] | + | [[Category: Panda SP]] |
| - | [[Category: Xia, C.]] | + | [[Category: Xia C]] |
| - | [[Category: Cytochrome p450 reductase]]
| + | |
| - | [[Category: Fad]]
| + | |
| - | [[Category: Flavoprotein]]
| + | |
| - | [[Category: Fmn]]
| + | |
| - | [[Category: Human cypor]]
| + | |
| - | [[Category: Nadph]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Disease
NCPR_HUMAN Defects in POR are the cause of Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis (ABS1) [MIM:201750. A disease characterized by the association of Antley-Bixler syndrome with steroidogenesis defects and abnormal genitalia. Antley-Bixler syndrome is characterized by craniosynostosis, radiohumeral synostosis present from the perinatal period, midface hypoplasia, choanal stenosis or atresia, femoral bowing and multiple joint contractures.[1] [2] [3] Defects in POR are the cause of disordered steroidogenesis due to cytochrome P450 oxidoreductase deficiency (DISPORD) [MIM:613571. A disorder resulting in a rare variant of congenital adrenal hyperplasia, with apparent combined P450C17 and P450C21 deficiency and accumulation of steroid metabolites. Affected girls are born with ambiguous genitalia, but their circulating androgens are low and virilization does not progress. Conversely, affected boys are sometimes born undermasculinized. Boys and girls can present with bone malformations, in some cases resembling the pattern seen in patients with Antley-Bixler syndrome.[4] [5]
Function
NCPR_HUMAN This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5.
See Also
References
- ↑ Adachi M, Tachibana K, Asakura Y, Yamamoto T, Hanaki K, Oka A. Compound heterozygous mutations of cytochrome P450 oxidoreductase gene (POR) in two patients with Antley-Bixler syndrome. Am J Med Genet A. 2004 Aug 1;128A(4):333-9. PMID:15264278 doi:10.1002/ajmg.a.30169
- ↑ Fukami M, Horikawa R, Nagai T, Tanaka T, Naiki Y, Sato N, Okuyama T, Nakai H, Soneda S, Tachibana K, Matsuo N, Sato S, Homma K, Nishimura G, Hasegawa T, Ogata T. Cytochrome P450 oxidoreductase gene mutations and Antley-Bixler syndrome with abnormal genitalia and/or impaired steroidogenesis: molecular and clinical studies in 10 patients. J Clin Endocrinol Metab. 2005 Jan;90(1):414-26. Epub 2004 Oct 13. PMID:15483095 doi:jc.2004-0810
- ↑ Fluck CE, Tajima T, Pandey AV, Arlt W, Okuhara K, Verge CF, Jabs EW, Mendonca BB, Fujieda K, Miller WL. Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome. Nat Genet. 2004 Mar;36(3):228-30. Epub 2004 Feb 1. PMID:14758361 doi:10.1038/ng1300
- ↑ Fluck CE, Tajima T, Pandey AV, Arlt W, Okuhara K, Verge CF, Jabs EW, Mendonca BB, Fujieda K, Miller WL. Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome. Nat Genet. 2004 Mar;36(3):228-30. Epub 2004 Feb 1. PMID:14758361 doi:10.1038/ng1300
- ↑ Arlt W, Walker EA, Draper N, Ivison HE, Ride JP, Hammer F, Chalder SM, Borucka-Mankiewicz M, Hauffa BP, Malunowicz EM, Stewart PM, Shackleton CH. Congenital adrenal hyperplasia caused by mutant P450 oxidoreductase and human androgen synthesis: analytical study. Lancet. 2004 Jun 26;363(9427):2128-35. PMID:15220035 doi:10.1016/S0140-6736(04)16503-3
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