Cytochrome P450: Difference between revisions

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[[Image:2f9q.png|left|200px|thumb|Crystal Structure of Cytochrome P450 [[2f9q]]]]
<StructureSection load='' size='350' side='right' caption='Cytochrome P450 CypC2 with heme C complex with warfarin (PDB entry [[1og5]])' scene='43/430105/Cv/2'>
{{STRUCTURE_2f9q|  PDB=2f9q  | SIZE=300| SCENE=Cytochrome_P450/Cv/1 |right|CAPTION=Cytochrome P450 with heme and sulfate ions [[2f9q]] }}
__TOC__
== Function ==


[[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]]).
[[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'''.
* '''P450cam''', also known as camphor 5-monooxygenase, catalyzes the hydroxylation of camphor<ref>PMID:10698731</ref>.<br />
* '''P450nor''' is a Nitric Oxide Reductase P450<ref>PMID:15598501</ref>.<br />
* '''P450epoK''' converts epothilone D to epothilone B<ref>PMID:12933799</ref>.<br />
* '''P450cin''' monooxygenates 1,8-cineole which is similar to camphor<ref>PMID:26002741</ref>.<br />
*  '''Bifunctional P450/NADPH P450 reductase''' (P450 BM3) is a fatty acid monooxygenase.<br />
*  '''P450 3A4''' see [[CYP3A4]].<br />
*  '''P450 19 family''' see [[Aromatase]].<br />
* '''P450 17A1''' see [[Abiraterone acetate|Human steroidogenic cytochrome P450 17A1 with inhibitor abiraterone]]
See also [[Hemeproteins]].


{{TOC limit|limit=2}}
Additional details on cytochrome P450 interactions with drugs see
*[[Drug Metabolism by CYP450 Enzymes]]<br />
*[[Montelukast]] - anti rhinitis
*[[Noxafil]] - antifungal drug which binds to CYP51.
*[[Antifungal drugs]] - antifungal drugs which binds to CYP51.
*[[Cobicistat]] - anti HIV/AIDS drug which binds to CYP3A4.
*[[Cytochrome P450 inhibitors]]


== 3D Structures of Cytochrome P450  ==
== Structural highlights ==


''Update June 2011''
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>


=== human P4501 family ===
== 3D Structures of Cytochrome P450  ==
[[Cytochrome P450  3D structures]]
[[2hi4]] – hP4501A2+naphthoflavone - human<br />
[[3pm0]] - hP4501B1+naphthoflavone<br />
 
=== human P4502 family ===
[[3gph]], [[3koh]], [[3lc4]]  – hP4502E1 fragment +imidazole derivative<br />
[[3e6i]] – hP4502E1 fragment+indazole<br />
[[3ebs]] – hP4502A6 (mutant)+phenacetin<br />
[[2fdu]], [[2fdv]], [[2fdw]], [[2fdy]] - hP4502A6+pyridine derivative<br />
[[1z10]] - hP4502A6 catalytic domain+coumarin<br />
[[3e4e]] – hP4502E1 fragment+methylpyrazole<br />
[[3czh]], [[3dl9]], [[3c6g]] – hP4502R1+vitamin D<br />
[[2nnh]] – hP4502C8+retinoic acid<br />
[[2nni]] - hP4502C8+montelukast<br />
[[2nnj]] - hP4502C8+felodipine<br />
[[1pq2]] - hP4502C8<br />
[[1og2]], [[1og5]] – hP4502C9 (mutant)<br />
[[1r9o]] – hP4502C9 (mutant)+flurbiprofen<br />
[[2pg5]], [[2pg6]], [[2pg7]] – hP4502A6 (mutant)<br />
[[2p85]] – hP4502A13 (mutant)+indole<br />
[[3ibd]] – hP4502B6 (mutant)+4-(4-chlorophenyl)imidazole<br />
[[2f9q]] – hP4502D6<br />
[[2z10]] – hP4502A6+coumarin<br />
[[1z11]] - hP4502A6+methoxalen
 
 
=== human P4503 family ===
 
[[2v0m]] – hP4503A4+ketoconazole<br />
[[2j0d]] - hP4503A4+erythromycin<br />
[[3nxu]] - hP4503A4+ritonavir<br />
[[1tqn]], [[1w0e]], [[1w0f]], [[1w0g]] – hP4503A4<br />
 
 
=== human P4507 family ===
 
[[3dax]] – hP4507A1
 
 
=== human P45019 family ===
 
[[3eqm]] - hP45019A1+androstenedione
 
 
=== human P45046 family ===
 
[[2q9f]] – hP45046A1+cholesterol<br />
[[2q9d]], [[2q9g]] - hP45046A1<br />
[[2vn0]] – hP450105A1+troglitazone<br />
[[2zby]] - hP450105A1 (mutant)
 
 
=== P450 from ''Mycobacterium tuberculosis'' ===
 
[[2vku]], [[1h5z]] – MtP45051 - ''Mycobacterium tuberculosis''<br />
[[2ci0]], [[2cib]], [[1u13]] - MtP45051 (mutant)<br />
[[1x8v]] - MtP45051 (mutant)+estriol<br />
[[1ea1]] - MtP45051 (mutant)+ fluconazole<br />
[[1e9x]] - MtP45051 (mutant)+ phenylimidazole<br />
[[3cxv]], [[3cxx]], [[3cxy]], [[3cxz]], [[3cy0]], [[3cy1]] - MtP450121 (mutant)<br />
[[3g5f]], [[3g5h]], [[2ij5]], [[1n40]] – MtP450121<br />
[[2ij7]] - MtP450121+fluconazole<br />
[[1n4g]] - MtP450121+iodopyrazole<br />
[[3ivi]], [[3iw0]], [[3ivy]] – MtP450125 <br />
[[3iw1]] - MtP450125+androstenedione<br />
[[3iw2]] - MtP450125+econazole<br />
[[2uvn]] - MtP450130+econazole<br />
[[2wgy]] – MtP450130 (mutant)<br />
[[2w09]], [[2w0b]], [[2w0a]] - MtP450130 (mutant)+pyridine inhibitor<br />
[[2uuq]] – MtP450130
 
 
 
=== P450cam ===
 
[[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 />
[[1dz4]], [[1dz8]], [[1dz6]], [[1dz9]], [[5cp4]], [[1phc]], [[2cpp]], [[1yrc]], [[1yrd]], [[3l61]], [[3l62]], [[3l63]] - PpP450cam<br />
[[2qbo]] - PpP450cam (mutant)+cyanide<br />
[[1qmq]] - PpP450cam (mutant)+Ru substrate<br />
[[2h7q]] - PpP450cam+imidazole<br />
[[1cp4]] - PpP450cam+benzene<br />
[[1akd]], [[1iwi]], [[1noo]], [[7cpp]], [[8cpp]], [[2zwt]], [[2zwu]] - PpP450cam+1S-camphor derivative<br />
[[1iwj]], [[1iwk]], [[2zuh]], [[2zui]], [[2zuj]], [[3fwf]], [[3fwg]], [[3fwi]], [[3fwj]] - PpP450cam (mutant)+1Scamphor<br />
[[2l8m]] – PpP450cam+camphor+CO<br />
[[2fe6]], [[2fer]], [[2feu]] - PpP450cam+Mn protoporphyrin IX<br />
[[1uyu]] - PpP450cam+ Xe<br />
[[1o76]] - PpP450cam+cyanide<br />
[[4cpp]] - PpP450cam+adamantine<br />
[[5cpp]] - PpP450cam+adamantanone<br />
[[6cpp]] - PpP450cam+camphene<br />
[[1p2y]], [[1p7r]] - PpP450cam+nicotine<br />
[[1re9]], [[1rf9]] - PpP450cam +fluorescent probe<br />
[[2z97]], [[2zaw]], [[2zax]] - PpP450cam+methyl depropionated hemin<br />
[[3cpp]] - PpP450cam+CO<br />
[[1pha]], [[1phb]], [[1phd]], [[1phe]], [[1phf]], [[1phg]] - PpP450cam+imidazole derivative<br />
[[1gek]], [[1gem]] - PpP450cam+N-butyl-isocyanide<br />
[[1lwl]] - PpP450cam+fluorescent probe<br />
[[2h7r]] - PpP450cam (mutant)+imidazole<br />
[[1k2o]] - PpP450cam (mutant)+pyridine derivative<br />
[[1gjm]] - PpP450cam (mutant)+sulphydryl reagent<br />
[[2a1m]], [[2a1n]], [[2a10]] - PpP450cam (mutant)+ferrous dioxygen<br />
[[1t85]], [[1t86]], [[1t87]], [[1t88]] - PpP450cam (mutant)+ferrous CO<br />
[[1j51]] - PpP450cam (mutant)+trichlorobenzene<br />
[[1mpw]] - PpP450cam (mutant)+trimethylbicycloheptene<br />
[[3oia]], [[3ol5]], [[3p6m]], [[3p6n]], [[3p6o]], [[3p6p]], [[3poq]], [[3por]], [[3pos]], [[3pot]], [[3pou]], [[3pov]], [[3pow]], [[3pox]] - PpP450cam (mutant)+substrate analog<br />
 
 
=== P450nor ===
 
[[1cl6]], [[1rom]] – FoP450nor - ''Fusarium oxysporum''<br />
[[2rom]] - FoP450nor+CO<br />
[[1cmj]], [[1cmn]], [[1ehg]] - FoP450nor (mutant)<br />
[[1xqd]] – FoP450nor+pyridinealdehyde adenine<br />
[[1jfb]], [[1jfc]], [[1ged]], [[1ehe]] - FoP450nor<br />
[[1gej]], [[1gei]] - FoP450nor+N-butyl-isocyanide<br />
[[1ulw]] - FoP450nor  (mutant)
 
===P450epoK===
 
[[1pfk]] – P450epoK+epothilone D – ''Sorangium cellulosum''
 
===P450cin===
 
[[3bdz]], [[3be0]] – P450cin – ''Citrobacter braakii''
 
=== rabbit P450 ===
 
[[2bdm]] – rP4502B4 – rabbit<br />
[[1po5]], [[3mvr]], [[3r1a]], [[3r1b]] - rP4502B4 (mutant)<br />
[[1suo]] - rP4502B4 (mutant)+imidazole<br />
[[3kw4]], [[3me6]] - rP4502B4 (mutant)+anti-platelet drug<br />
[[1dt6]] - rP4502C5 (mutant)<br />
[[1nr6]] – rP4502C5+diclofenac<br />
[[1n6b]] - rP4502C5+sulfaphenazole
 
 
=== Other CYPs ===


[[1ued]] – AoP450 oxyC – ''Amycolatopsis orientalis''<br />
</StructureSection>
[[1lfk]], [[1lg9]], [[1lgf]] - AoP450 oxyB<br />
[[1q5d]] – ScP450EPOK+epothilone – ''Sorangium cellulosum''<br />
[[1q5e]] - ScP450EPOK<br />
[[1io8]] – SsP450119 (mutant) – ''Sulfolobus solfataricus''<br />
[[1io9]], [[1io7]], [[1f4u]] - SsP450119<br />
[[1f4t]] - SsP450119+ phenylimidazole<br />
[[1cpt]] – P450108 – ''Pseudomonas sp.''<br />
[[2uwh]] - BmP450102+palmitic acid<br />
[[3ekb]], [[3ekd]], [[3ekf]], [[2ij3]], [[2ij4]] - BmP450102 heme domain (mutant)<br />
[[2ij2]], [[2hpd]] - BmP450102 heme domain<br />
[[3ben]] - BmP450102 + imidazole derivative<br />
[[2j1m]], [[2j4s]] - BmP450102+DMSO<br />
[[1bvy]], [[1bu7]] – BmP450102A1 FMN domain<br />
[[1fag]] – BmP450102A1+ palmitic acid<br />
[[1fah]] – BmP450102A1 (mutant)<br />
[[2bmh]] - BmP450102A1<br />
[[3aba]] – SaP450105P1+filipin I – ''Streptomyces avermitilis''<br />
[[3abb]] – SaP450105D6<br />
[[3e5j]], [[3e5l]] - SaP450105P1 (mutant)<br />
[[3e5k]] - SaP450105P1 (mutant)+4-phenylimidazole<br />
[[2whw]], [[2wi9]], [[2vz7]] – SvP450107L1 (mutant) – ''Streptomyces venezuelae''<br />
[[2vzm]] – SvP450107L1 (mutant)+narbomycin<br />
[[2c7x]] - SvP450107L1+narbomycin<br />
[[2cd8]], [[2ca0]], [[2c6h]] – SvP450107L1+YC-17<br />
[[2bvj]] - SvP450107L1<br />
[[3p3l]], [[3p3o]], [[3p3x]], [[3p3z]] – P450 – ''Streptomyces thioluteus''<br />
[[2zqj]] – BsP450152A1 – ''Bacillus subtilis''<br />
[[2zqx]] - BsP450152A1+heptanoic acid<br />
[[3nc3]], [[3nc5]], [[3nc6]], [[3nc7]] - BsP450134A1 (mutant)<br />
[[1izo]] – BsP450 BS beta+ palmitoleic acid<br />
[[1jin]], [[1jip]] - SeP450107A1+ ketoconazole - ''Saccharopolyspora erythraea''<br />
[[1jio]], [[1oxa]] - SeP450107A1+6DEB<br />
[[1eup]] – SeP450107A1+androstendione<br />
[[1egy]] - SeP450107A1+aminophenanthrene<br />
[[2jjn]], [[2jjo]] - SeP450113A1 (mutant)<br />
[[2jjp]] - SeP450113A1 (mutant)+ketoconazole<br />
[[2vrv]] - SeP450113A1 (mutant)+clotrimazole<br />
[[3a1l]] – SsP450245A1+dichlorochrompyrrolic acid – ''Streptomyces sp.''<br />
[[2z3t]] - SsP450245A1<br />
[[2z3u]] - SsP450245A1+chromopyrrolic acid<br />
[[3g5n]], [[3g93]] – rCYP2B4 (mutant)+1-biphenyl-4-methyl-1H-imidazole – rabbit<br />
[[2q6n]] – rP4502B4 (mutant)+chlorophenyl-imidazole<br />
[[3cv8]] – SgP450105A1 (mutant) – ''Streptomyces griseolus''<br />
[[3cv9]], [[2zbz]] - SgP450105A1 (mutant)+vitamin D3<br />
[[2zbx]] - SgP450105A1+imidazole<br />
[[3dam]], [[3dan]], [[3dbm]] – P45074A2 – ''Parthenium argentatum''<br />
[[2rch]], [[3dsi]] – AtP45074A+13(S)-HOD – ''Arabidopsis thaliana''<br />
[[3dsj]] - AtP45074A (mutant)+13(S)-HOD<br />
[[2rcl]] - AtP45074A+vernolic acid<br />
[[3dsk]] - AtP45074A (mutant)+ vernolic acid<br />
[[2rcm]], [[3cli]] - AtP45074A<br />
[[2rfb]] – PtP450 – ''Picrophilus torridus''<br />
[[2rfc]] – PtP450+phenylimidazole<br />
[[2nz5]], [[2nza]], [[2dkk]] – ScP450158A1 – ''Streptomyces coelicolor''<br />
[[1gwi]] - ScP450154C1<br />
[[1wiy]] – TtP450 – ''Thermus thermophilus''<br />
[[1n97]] – TtP450175A1<br />
[[3lxh]], [[3lxi]], [[3ofu]] – NaP240101D1 – ''Novosphingobium aromaticivorans''<br />
[[3nv5]], [[3nv6]] - NaP240101D2<br />


== References ==
<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]
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