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Cytochrome P450

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[[Image:2f9q.png|left|200px|thumb|Crystal Structure of Cytochrome P450 [[2f9q]]]]
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<StructureSection load='' size='350' side='right' caption='Cytochrome P450 CypC2 with heme C complex with warfarin (PDB entry [[1og5]])' scene='43/430105/Cv/2'>
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{{STRUCTURE_2f9q| PDB=2f9q | SIZE=300| SCENE=Cytochrome_P450/Cv/1 |right|CAPTION=Cytochrome P450 with heme and sulfate ions [[2f9q]] }}
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__TOC__
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== Function ==
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[[Cytochrome P450]] (P450) catalyzes the oxidation of organic substances like lipids. catalyzes the oxidation of organic substances like lipids. The P450 contains a heme cofactor. The protein is numbered by its gene. P450cam, also known as camphor 5-monooxygenase, catalyzes the hydroxylation of camphor. P450nor is a Nitric Oxide Reductase P450. P450epoK converts epothilone D to epothilone B. P450cin monooxygenates 1,8-cineole which is similar to camphor. The images at the left and at the right correspond to one representative P450, ''i.e.'' the crystal structure of human P4502 ([[2f9q]]).
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[[Cytochrome P450]] (P450) or '''cytochrome P450 monooxygenase''' catalyzes the oxidation of organic substances like lipids. The P450 contains a heme cofactor. The protein is numbered by its gene.<ref>PMID:12369887</ref> P450 CYP121 is called '''mycocyclosin synthase'''.
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* '''P450cam''', also known as camphor 5-monooxygenase, catalyzes the hydroxylation of camphor<ref>PMID:10698731</ref>.<br />
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* '''P450nor''' is a Nitric Oxide Reductase P450<ref>PMID:15598501</ref>.<br />
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* '''P450epoK''' converts epothilone D to epothilone B<ref>PMID:12933799</ref>.<br />
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* '''P450cin''' monooxygenates 1,8-cineole which is similar to camphor<ref>PMID:26002741</ref>.<br />
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* '''Bifunctional P450/NADPH P450 reductase''' (P450 BM3) is a fatty acid monooxygenase.<br />
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* '''P450 3A4''' see [[CYP3A4]].<br />
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* '''P450 19 family''' see [[Aromatase]].<br />
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* '''P450 17A1''' see [[Abiraterone acetate|Human steroidogenic cytochrome P450 17A1 with inhibitor abiraterone]]
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See also [[Hemeproteins]].
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{{TOC limit|limit=2}}
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Additional details on cytochrome P450 interactions with drugs see
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*[[Drug Metabolism by CYP450 Enzymes]]<br />
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*[[Montelukast]] - anti rhinitis
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*[[Noxafil]] - antifungal drug which binds to CYP51.
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*[[Antifungal drugs]] - antifungal drugs which binds to CYP51.
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*[[Cobicistat]] - anti HIV/AIDS drug which binds to CYP3A4.
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*[[Cytochrome P450 inhibitors]]
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== 3D Structures of Cytochrome P450 ==
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== Structural highlights ==
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''Update June 2011''
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The <scene name='43/430105/Cv/6'>heme moiety is stabilized by several side chains</scene>. The <scene name='43/430105/Cv/7'>heme iron is pentacoordinated with Cys as one ligand</scene>.<ref>PMID:12861225</ref>
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=== human P4501 family ===
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== 3D Structures of Cytochrome P450 ==
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[[Cytochrome P450 3D structures]]
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[[2hi4]] – hP4501A2+naphthoflavone - human<br />
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[[3pm0]] - hP4501B1+naphthoflavone<br />
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=== human P4502 family ===
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[[3gph]], [[3koh]], [[3lc4]] – hP4502E1 fragment +imidazole derivative<br />
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[[3e6i]] – hP4502E1 fragment+indazole<br />
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[[3ebs]] – hP4502A6 (mutant)+phenacetin<br />
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[[2fdu]], [[2fdv]], [[2fdw]], [[2fdy]] - hP4502A6+pyridine derivative<br />
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[[1z10]] - hP4502A6 catalytic domain+coumarin<br />
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[[3e4e]] – hP4502E1 fragment+methylpyrazole<br />
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[[3czh]], [[3dl9]], [[3c6g]] – hP4502R1+vitamin D<br />
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[[2nnh]] – hP4502C8+retinoic acid<br />
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[[2nni]] - hP4502C8+montelukast<br />
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[[2nnj]] - hP4502C8+felodipine<br />
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[[1pq2]] - hP4502C8<br />
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[[1og2]], [[1og5]] – hP4502C9 (mutant)<br />
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[[1r9o]] – hP4502C9 (mutant)+flurbiprofen<br />
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[[2pg5]], [[2pg6]], [[2pg7]] – hP4502A6 (mutant)<br />
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[[2p85]] – hP4502A13 (mutant)+indole<br />
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[[3ibd]] – hP4502B6 (mutant)+4-(4-chlorophenyl)imidazole<br />
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[[2f9q]] – hP4502D6<br />
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[[2z10]] – hP4502A6+coumarin<br />
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[[1z11]] - hP4502A6+methoxalen
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=== human P4503 family ===
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[[2v0m]] – hP4503A4+ketoconazole<br />
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[[2j0d]] - hP4503A4+erythromycin<br />
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[[3nxu]] - hP4503A4+ritonavir<br />
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[[1tqn]], [[1w0e]], [[1w0f]], [[1w0g]] – hP4503A4<br />
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=== human P4507 family ===
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[[3dax]] – hP4507A1
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=== human P45019 family ===
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[[3eqm]] - hP45019A1+androstenedione
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=== human P45046 family ===
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[[2q9f]] – hP45046A1+cholesterol<br />
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[[2q9d]], [[2q9g]] - hP45046A1<br />
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[[2vn0]] – hP450105A1+troglitazone<br />
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[[2zby]] - hP450105A1 (mutant)
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=== P450 from ''Mycobacterium tuberculosis'' ===
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[[2vku]], [[1h5z]] – MtP45051 - ''Mycobacterium tuberculosis''<br />
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[[2ci0]], [[2cib]], [[1u13]] - MtP45051 (mutant)<br />
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[[1x8v]] - MtP45051 (mutant)+estriol<br />
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[[1ea1]] - MtP45051 (mutant)+ fluconazole<br />
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[[1e9x]] - MtP45051 (mutant)+ phenylimidazole<br />
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[[3cxv]], [[3cxx]], [[3cxy]], [[3cxz]], [[3cy0]], [[3cy1]] - MtP450121 (mutant)<br />
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[[3g5f]], [[3g5h]], [[2ij5]], [[1n40]] – MtP450121<br />
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[[2ij7]] - MtP450121+fluconazole<br />
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[[1n4g]] - MtP450121+iodopyrazole<br />
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[[3ivi]], [[3iw0]] – MtP450125 <br />
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[[3iw1]] - MtP450125+androstenedione<br />
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[[3iw2]] - MtP450125+econazole<br />
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[[2uvn]] - MtP450130+econazole<br />
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[[2wgy]] – MtP450130 (mutant)<br />
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[[2w09]], [[2w0b]], [[2w0a]] - MtP450130 (mutant)+pyridine inhibitor<br />
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[[2uuq]] – MtP450130
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=== P450cam ===
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[[2qbl]], [[2qbm]], [[2qbn]], [[2gqx]], [[2gr6]], [[2frz]], [[2h7s]], [[6cp4]], [[2cp4]], [[3cp4]], [[4cp4]], [[1c8j]], [[1geb]], [[2a1o]],[[3p6q]], [[3p6r]], [[3p6s]], [[3p6t]], [[3p6u]], [[3p6v]], [[3p6w]], [[3p6x]]– PpP450cam(mutant) – ''Pseudomona putida''<br />
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[[1dz4]], [[1dz8]], [[1dz6]], [[1dz9]], [[5cp4]], [[1phc]], [[2cpp]], [[1yrc]], [[1yrd]], [[3l61]], [[3l62]], [[3l63]] - PpP450cam<br />
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[[2qbo]] - PpP450cam (mutant)+cyanide<br />
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[[1qmq]] - PpP450cam (mutant)+Ru substrate<br />
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[[2h7q]] - PpP450cam+imidazole<br />
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[[1cp4]] - PpP450cam+benzene<br />
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[[1akd]], [[1iwi]], [[1noo]], [[7cpp]], [[8cpp]], [[2zwt]], [[2zwu]] - PpP450cam+1S-camphor derivative<br />
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[[1iwj]], [[1iwk]], [[2zuh]], [[2zui]], [[2zuj]], [[3fwf]], [[3fwg]], [[3fwi]], [[3fwj]] - PpP450cam (mutant)+1Scamphor<br />
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[[2fe6]], [[2fer]], [[2feu]] - PpP450cam+Mn protoporphyrin IX<br />
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[[1uyu]] - PpP450cam+ Xe<br />
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[[1o76]] - PpP450cam+cyanide<br />
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[[4cpp]] - PpP450cam+adamantine<br />
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[[5cpp]] - PpP450cam+adamantanone<br />
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[[6cpp]] - PpP450cam+camphene<br />
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[[1p2y]], [[1p7r]] - PpP450cam+nicotine<br />
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[[1re9]], [[1rf9]] - PpP450cam +fluorescent probe<br />
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[[2z97]], [[2zaw]], [[2zax]] - PpP450cam+methyl depropionated hemin<br />
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[[3cpp]] - PpP450cam+CO<br />
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[[1pha]], [[1phb]], [[1phd]], [[1phe]], [[1phf]], [[1phg]] - PpP450cam+imidazole derivative<br />
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[[1gek]], [[1gem]] - PpP450cam+N-butyl-isocyanide<br />
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[[1lwl]] - PpP450cam+fluorescent probe<br />
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[[2h7r]] - PpP450cam (mutant)+imidazole<br />
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[[1k2o]] - PpP450cam (mutant)+pyridine derivative<br />
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[[1gjm]] - PpP450cam (mutant)+sulphydryl reagent<br />
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[[2a1m]], [[2a1n]], [[2a10]] - PpP450cam (mutant)+ferrous dioxygen<br />
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[[1t85]], [[1t86]], [[1t87]], [[1t88]] - PpP450cam (mutant)+ferrous CO<br />
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[[1j51]] - PpP450cam (mutant)+trichlorobenzene<br />
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[[1mpw]] - PpP450cam (mutant)+trimethylbicycloheptene<br />
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[[3oia]], [[3ol5]], [[3p6m]], [[3p6n]], [[3p6o]], [[3p6p]], [[3poq]], [[3por]], [[3pos]], [[3pot]], [[3pou]], [[3pov]], [[3pow]], [[3pox]] - PpP450cam (mutant)+substrate analog<br />
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=== P450nor ===
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[[1cl6]], [[1rom]] – FoP450nor - ''Fusarium oxysporum''<br />
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[[2rom]] - FoP450nor+CO<br />
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[[1cmj]], [[1cmn]], [[1ehg]] - FoP450nor (mutant)<br />
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[[1xqd]] – FoP450nor+pyridinealdehyde adenine<br />
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[[1jfb]], [[1jfc]], [[1ged]], [[1ehe]] - FoP450nor<br />
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[[1gej]], [[1gei]] - FoP450nor+N-butyl-isocyanide<br />
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[[1ulw]] - FoP450nor (mutant)
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===P450epoK===
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[[1pfk]] – P450epoK+epothilone D – ''Sorangium cellulosum''
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===P450cin===
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[[3bdz]], [[3be0]] – P450cin – ''Citrobacter braakii''
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=== rabbit P450 ===
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[[2bdm]] – rP4502B4 – rabbit<br />
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[[1po5]], [[3mvr]], [[3r1a]], [[3r1b]] - rP4502B4 (mutant)<br />
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[[1suo]] - rP4502B4 (mutant)+imidazole<br />
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[[3kw4]], [[3me6]] - rP4502B4 (mutant)+anti-platelet drug<br />
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[[1dt6]] - rP4502C5 (mutant)<br />
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[[1nr6]] – rP4502C5+diclofenac<br />
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[[1n6b]] - rP4502C5+sulfaphenazole
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=== Other CYPs ===
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[[1ued]] – AoP450 oxyC – ''Amycolatopsis orientalis''<br />
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</StructureSection>
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[[1lfk]], [[1lg9]], [[1lgf]] - AoP450 oxyB<br />
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[[1q5d]] – ScP450EPOK+epothilone – ''Sorangium cellulosum''<br />
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[[1q5e]] - ScP450EPOK<br />
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[[1io8]] – SsP450119 (mutant) – ''Sulfolobus solfataricus''<br />
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[[1io9]], [[1io7]], [[1f4u]] - SsP450119<br />
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[[1f4t]] - SsP450119+ phenylimidazole<br />
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[[1cpt]] – P450108 – ''Pseudomonas sp.''<br />
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[[2uwh]] - BmP450102+palmitic acid<br />
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[[3ekb]], [[3ekd]], [[3ekf]], [[2ij3]], [[2ij4]] - BmP450102 heme domain (mutant)<br />
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[[2ij2]], [[2hpd]] - BmP450102 heme domain<br />
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[[3ben]] - BmP450102 + imidazole derivative<br />
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[[2j1m]], [[2j4s]] - BmP450102+DMSO<br />
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[[1bvy]], [[1bu7]] – BmP450102A1 FMN domain<br />
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[[1fag]] – BmP450102A1+ palmitic acid<br />
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[[1fah]] – BmP450102A1 (mutant)<br />
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[[2bmh]] - BmP450102A1<br />
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[[3aba]] – SaP450105P1+filipin I – ''Streptomyces avermitilis''<br />
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[[3abb]] – SaP450105D6<br />
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[[3e5j]], [[3e5l]] - SaP450105P1 (mutant)<br />
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[[3e5k]] - SaP450105P1 (mutant)+4-phenylimidazole<br />
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[[2whw]], [[2wi9]], [[2vz7]] – SvP450107L1 (mutant) – ''Streptomyces venezuelae''<br />
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[[2vzm]] – SvP450107L1 (mutant)+narbomycin<br />
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[[2c7x]] - SvP450107L1+narbomycin<br />
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[[2cd8]], [[2ca0]], [[2c6h]] – SvP450107L1+YC-17<br />
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[[2bvj]] - SvP450107L1<br />
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[[2zqj]] – BsP450152A1 – ''Bacillus subtilis''<br />
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[[2zqx]] - BsP450152A1+heptanoic acid<br />
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[[3nc3]], [[3nc5]], [[3nc6]], [[3nc7]] - BsP450134A1 (mutant)<br />
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[[1izo]] – BsP450 BS beta+ palmitoleic acid<br />
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[[1jin]], [[1jip]] - SeP450107A1+ ketoconazole - ''Saccharopolyspora erythraea''<br />
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[[1jio]], [[1oxa]] - SeP450107A1+6DEB<br />
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[[1eup]] – SeP450107A1+androstendione<br />
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[[1egy]] - SeP450107A1+aminophenanthrene<br />
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[[2jjn]], [[2jjo]] - SeP450113A1 (mutant)<br />
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[[2jjp]] - SeP450113A1 (mutant)+ketoconazole<br />
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[[2vrv]] - SeP450113A1 (mutant)+clotrimazole<br />
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[[3a1l]] – SsP450245A1+dichlorochrompyrrolic acid – ''Streptomyces sp.''<br />
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[[2z3t]] - SsP450245A1<br />
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[[2z3u]] - SsP450245A1+chromopyrrolic acid<br />
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[[3g5n]], [[3g93]] – rCYP2B4 (mutant)+1-biphenyl-4-methyl-1H-imidazole – rabbit<br />
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[[2q6n]] – rP4502B4 (mutant)+chlorophenyl-imidazole<br />
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[[3cv8]] – SgP450105A1 (mutant) – ''Streptomyces griseolus''<br />
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[[3cv9]], [[2zbz]] - SgP450105A1 (mutant)+vitamin D3<br />
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[[2zbx]] - SgP450105A1+imidazole<br />
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[[3dam]], [[3dan]], [[3dbm]] – P45074A2 – ''Parthenium argentatum''<br />
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[[2rch]], [[3dsi]] – AtP45074A+13(S)-HOD – ''Arabidopsis thaliana''<br />
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[[3dsj]] - AtP45074A (mutant)+13(S)-HOD<br />
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[[2rcl]] - AtP45074A+vernolic acid<br />
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[[3dsk]] - AtP45074A (mutant)+ vernolic acid<br />
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[[2rcm]], [[3cli]] - AtP45074A<br />
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[[2rfb]] – PtP450 – ''Picrophilus torridus''<br />
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[[2rfc]] – PtP450+phenylimidazole<br />
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[[2nz5]], [[2nza]], [[2dkk]] – ScP450158A1 – ''Streptomyces coelicolor''<br />
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[[1gwi]] - ScP450154C1<br />
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[[1wiy]] – TtP450 – ''Thermus thermophilus''<br />
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[[1n97]] – TtP450175A1<br />
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[[3lxh]], [[3lxi]], [[3ofu]] – NaP240101D1 – ''Novosphingobium aromaticivorans''<br />
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[[3nv5]], [[3nv6]] - NaP240101D2<br />
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== References ==
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<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Cytochrome P450 CypC2 with heme C complex with warfarin (PDB entry 1og5)

Drag the structure with the mouse to rotate

References

  1. ↑ Danielson PB. The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism in humans. Curr Drug Metab. 2002 Dec;3(6):561-97. PMID:12369887
  2. ↑ Schlichting I, Berendzen J, Chu K, Stock AM, Maves SA, Benson DE, Sweet RM, Ringe D, Petsko GA, Sligar SG. The catalytic pathway of cytochrome p450cam at atomic resolution. Science. 2000 Mar 3;287(5458):1615-22. PMID:10698731
  3. ↑ Daiber A, Shoun H, Ullrich V. Nitric oxide reductase (P450nor) from Fusarium oxysporum. J Inorg Biochem. 2005 Jan;99(1):185-93. PMID:15598501 doi:10.1016/j.jinorgbio.2004.09.018
  4. ↑ Nagano S, Li H, Shimizu H, Nishida C, Ogura H, Ortiz de Montellano PR, Poulos TL. Crystal structures of epothilone D-bound, epothilone B-bound, and substrate-free forms of cytochrome P450epoK. J Biol Chem. 2003 Nov 7;278(45):44886-93. Epub 2003 Aug 21. PMID:12933799 doi:http://dx.doi.org/10.1074/jbc.M308115200
  5. ↑ Stok JE, Slessor KE, Farlow AJ, Hawkes DB, De Voss JJ. Cytochrome P450cin (CYP176A1). Adv Exp Med Biol. 2015;851:319-39. PMID:26002741 doi:10.1007/978-3-319-16009-2_12
  6. ↑ Williams PA, Cosme J, Ward A, Angove HC, Matak Vinkovic D, Jhoti H. Crystal structure of human cytochrome P450 2C9 with bound warfarin. Nature. 2003 Jul 24;424(6947):464-8. Epub 2003 Jul 13. PMID:12861225 doi:http://dx.doi.org/10.1038/nature01862

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