Cytochrome P450: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older edit
No edit summary
Michal Harel (talk | contribs)
32,849 edits
No edit summary
 
(80 intermediate revisions by 3 users not shown)
Line 1: Line 1:
[[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 [[2f9q]] }}
__TOC__
== Function ==


Cytochrome P450 (CYP) catalyzes the oxidation of organic substances like lipids. The CYP contains a heme cofactor. The protein is numbered by its gene.  CYP-cam catalyzes the hydroxylation of camphor. P450nor is a Nitric Oxide Reductase CYP. The images at the left and at the right correspond to one representative CYP, ''i.e.'' the crystal structure of human CYP2 ([[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 ==


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>


== 3D Structures of Cytochrome P450  ==
[[Cytochrome P450  3D structures]]


=== CYP/P450 reductase ===
</StructureSection>
 
[[3kx3]], [[3kx4]], [[3kx5]], [[3hf2]], [[3dgi]], [[3cbd]], [[2nnb]], [[1zo4]], [[2yqo]], [[2yqp]], [[1smi]], [[1p0v]], [[1p0w]], [[1p0x]], [[1jme]] – BmCYP102A1/P450 reductase (mutant) – ''Bacilus megaterium''<br />
[[1zo9]] - BmCYP102A1/P450 reductase+N-palmitoylmethionine<br />
[[1zoa]], [[1jpz]] - BmCYP102A1/P450 reductase (mutant)+N-palmitoylglycine<br />
[[1smj]] - BmCYP102A1/P450 reductase (mutant)+N-palmitoleate
 
 
=== human CYP1 family ===
[[2hi4]] – hCYP1A2+naphthoflavone - human
 
 
=== human CYP2 family ===
[[3gph]], [[3koh]], [[3lc4]]  – hCYP2E1 fragment +imidazole derivative<br />
[[3e6i]] – hCYP2E1 fragment+indazole<br />
[[3ebs]] – hCYP2A6 (mutant)+phenacetin<br />
[[2fdu]], [[2fdv]], [[2fdw]], [[2fdy]] - hCYP2A6+pyridine derivative<br />
[[3e4e]] – hCYP2E1 fragment+methylpyrazole<br />
[[3czh]], [[3dl9]], [[3c6g]] – hCYP2R1+vitamin D<br />
[[2nnh]] – hCYP2C8+retinoic acid<br />
[[2nni]] - hCYP2C8+montelukast<br />
[[2nnj]] - hCYP2C8+felodipine<br />
[[1pq2]] - hCYP2C8<br />
[[1og2]], [[1og5]] – hCYP2C9 (mutant)<br />
[[1r9o]] – hCYP2C9 (mutant)+flurbiprofen<br />
[[2pg5]], [[2pg6]], [[2pg7]] – hCYP2A6 (mutant)<br />
[[2p85]] – hCYP2A13 (mutant)+indole<br />
[[3ibd]] – hCYP2B6 (mutant)+4-(4-chlorophenyl)imidazole<br />
[[2f9q]] – hCYP2D6<br />
[[2z10]] – hCYP2A6+coumarin<br />
[[1z11]] - hCYP2A6+methoxalen
 
 
=== human CYP3 family ===
 
[[2v0m]] – hCYP3A4+ketoconazole<br />
[[2j0d]] - hCYP3A4+erythromycin<br />
[[1tqn]], [[1w0e]], [[1w0f]], [[1w0g]] – hCYP3A4
 
 
=== human CYP7 family ===
 
[[3dax]] – hCYP7A1
 
 
=== human CYP19 family ===
 
[[3eqm]] - hCYP19A1+androstenedione
 
 
=== human CYP46 family ===
 
[[2q9f]] – hCYP46A1+cholesterol<br />
[[2q9d]] - hCYP46A1<br />
[[2vn0]] – hCYP105A1+troglitazone<br />
[[2zby]] - hCYP105A1 (mutant)
 
 
=== CYP from  ''Mycobacterium tuberculosis'' ===
 
[[2vku]], [[1h5z]] – MtCYP51 - ''Mycobacterium tuberculosis''<br />
[[2ci0]], [[2cib]], [[1u13]] - MtCYP51 (mutant)<br />
[[1x8v]] - MtCYP51 (mutant)+estriol<br />
[[1ea1]] - MtCYP51 (mutant)+ fluconazole<br />
[[1e9x]] - MtCYP51 (mutant)+ phenylimidazole<br />
[[3cxv]], [[3cxx]], [[3cxy]], [[3cxz]], [[3cy0]], [[3cy1]] - MtCYP121 (mutant)<br />
[[3g5f]], [[3g5h]], [[2ij5]], [[1n40]] – MtCYP121<br />
[[2ij7]] - MtCYP121+fluconazole<br />
[[1n4g]] - MtCYP121+iodopyrazole<br />
[[3ivi]], [[3iw0]] – MtCYP125 <br />
[[3iw1]] - MtCYP125+androstenedione<br />
[[3iw2]] - MtCYP125+econazole<br />
[[2uvn]] - MtCYP130+econazole<br />
[[2wgy]] – MtCYP130 (mutant)<br />
[[2w09]], [[2w0b]], [[2w0a]] - MtCYP130 (mutant)+pyridine inhibitor<br />
[[2uuq]] – MtCYP130
 
 
 
=== CYP-cam ===
 
[[2qbl]], [[2qbm]], [[2qbn]], [[2gqx]], [[2gr6]], [[2frz]], [[2h7s]], [[6cp4]], [[2cp4]], [[3cp4]], [[4cp4]] – PpCYP-cam (mutant) – ''Pseudomona putida''<br />
[[1dz4]], [[1dz8]], [[1dz6]], [[1dz9]], [[5cp4]], [[1phc]], [[2cpp]] - PpCYP-cam<br />
[[2qbo]] - PpCYP-cam (mutant)+cyanide<br />
[[1qmq]] - PpCYP-cam (mutant)+Ru substrate<br />
[[2h7q]] - PpCYP-cam+imidazole<br />
[[1cp4]] - PpCYP-cam+benzene<br />
[[1akd]] - PpCYP-cam+1S-camphor<br />
[[2fe6]], [[2fer]], [[2feu]] - PpCYP-cam+Mn protoporphyrin IX<br />
[[1uyu]] - PpCYP-cam + Xe<br />
[[1o76]] - PpCYP-cam +cyanide<br />
[[4cpp]] - PpCYP-cam+adamantine<br />
[[5cpp]] - PpCYP-cam+adamantanone<br />
[[6cpp]] - PpCYP-cam+camphene<br />
[[7cpp]] - PpCYP-cam+norcamphor<br />
[[8cpp]] - PpCYP-cam+thiocamphor<br />
[[3cpp]] - PpCYP-cam+CO<br />
[[1pha]], [[1phb]], [[1phd]], [[1phe]], [[1phf]], [[1phg]] - PpCYP-cam+imidazole derivative<br />
[[1gek]], [[1gem]] - PpCYP-cam +N-butyl-isocyanide<br />
[[1lwl]] - PpCYP-cam +fluorescent probe<br />
[[2h7r]] - PpCYP-cam (mutant)+imidazole<br />
[[1k2o]] - PpCYP-cam (mutant)+pyridine derivative<br />
[[1gjm]] - PpCYP-cam (mutant)+sulphydryl reagent<br />
[[2a1m]], [[2a1n]], [[2a10]] - PpCYP-cam (mutant)+ferrous dioxygen<br />
[[1t85]], [[1t86]], [[1t87]], [[1t88]] - PpCYP-cam (mutant)+ferrous CO
 
 
=== P450nor ===
 
[[1cl6]], [[1rom]] – FoP450nor - ''Fusarium oxysporum''<br />
[[2rom]] - FoP450nor+CO<br />
[[1cmj]], [[1cmn]] - FoP450nor (mutant)<br />
[[1xqd]] – FoP450nor+pyridinealdehyde adenine<br />
[[1jfb]], [[1jfc]], [[1ged]] - FoP450nor<br />
[[1gej]], [[1gei]] - FoP450nor+N-butyl-isocyanide<br />
[[1ulw]] - FoP450nor  (mutant)
 
 
 
=== rabbit CYP ===
 
[[2bdm]] – rCYP2B4 – rabbit<br />
[[1po5]] - rCYP2B4 (mutant)<br />
[[1suo]] - rCYP2B4 (mutant)+imidazole<br />
[[1dt6]] - rCYP2C5 (mutant)<br />
[[1nr6]] – rCYP2C5+diclofenac<br />
[[1n6b]] - rCYP2C5+sulfaphenazole
 
 
=== Other CYPs ===


[[1ued]] – AoCYP oxyC – ''Amycolatopsis orientalis''<br />
== References ==
[[1lfk]], [[1lg9]], [[1lgf]] - AoCYP oxyB<br />
<references/>
[[1q5d]] – ScCYPEPOK+epothilone – ''Sorangium cellulosum''<br />
[[Category:Topic Page]]
[[1q5e]] - ScCYPEPOK<br />
[[1io8]] – SsCYP119 (mutant) – ''Sulfolobus solfataricus''<br />
[[1io9]], [[1io7]], [[1f4u]] - SsCYP119<br />
[[1f4t]] - SsCYP119+ phenylimidazole<br />
[[1cpt]] – CYP108 – ''Pseudomonas sp.''<br />
[[2uwh]] - BmCYP102+palmitic acid<br />
[[3ekb]], [[3ekd]], [[3ekf]], [[2ij3]], [[2ij4]] - BmCYP102 heme domain (mutant)<br />
[[2ij2]], [[2hpd]] - BmCYP102 heme domain<br />
[[3ben]] - BmCYP102 + imidazole derivative<br />
[[2j1m]], [[2j4s]] - BmCYP102+DMSO<br />
[[1bvy]], [[1bu7]] – BmCYP102A1 FMN domain<br />
[[1fag]] – BmCYP102A1+ palmitic acid<br />
[[1fah]] – BmCYP102A1 (mutant)<br />
[[2bmh]] - BmCYP102A1<br />
[[3aba]] – SaCYP105P1+filipin I – ''Streptomyces avermitilis''<br />
[[3abb]] – SaCYP105D6<br />
[[3e5j]], [[3e5l]] - SaCYP105P1 (mutant)<br />
[[3e5k]] - SaCYP105P1 (mutant)+4-phenylimidazole<br />
[[2whw]], [[2wi9]], [[2vz7]] – SvCYP107L1 (mutant) – ''Streptomyces venezuelae''<br />
[[2vzm]] – SvCYP107L1 (mutant)+narbomycin<br />
[[2c7x]] - SvCYP107L1+narbomycin<br />
[[2cd8]], [[2ca0]], [[2c6h]] – SvCYP107L1+YC-17<br />
[[2bvj]] - SvCYP107L1<br />
[[2zqj]] – BsCYP152A1 – ''Bacillus subtilis''<br />
[[2zqx]] - BsCYP152A1+heptanoic acid<br />
[[1izo]] – BsCYP BS beta+ palmitoleic acid<br />
[[1jin]], [[1jip]] - SeCYP107A1+ ketoconazole - ''Saccharopolyspora erythraea''<br />
[[1jio]], [[1oxa]] - SeCYP107A1+6DEB<br />
[[1eup]] – SeCYP107A1+androstendione<br />
[[1egy]] - SeCYP107A1+aminophenanthrene<br />
[[2jjn]], [[2jjo]] - SeCYP113A1 (mutant)<br />
[[2jjp]] - SeCYP113A1 (mutant)+ketoconazole<br />
[[2vrv]] - SeCYP113A1 (mutant)+clotrimazole<br />
[[3a1l]] – SsCYP245A1+dichlorochrompyrrolic acid – ''Streptomyces sp.''<br />
[[2z3t]] - SsCYP245A1<br />
[[2z3u]] - SsCYP245A1+chromopyrrolic acid<br />
[[3g5n]], [[3g93]] – rCYP2B4 (mutant)+1-biphenyl-4-methyl-1H-imidazole – rabbit<br />
[[2q6n]] – rCYP2B4 (mutant)+chlorophenyl-imidazole<br />
[[3cv8]] – SgCYP105A1 (mutant) – ''Streptomyces griseolus''<br />
[[3cv9]], [[2zbz]] - SgCYP105A1 (mutant)+vitamin D3<br />
[[2zbx]] - SgCYP105A1+imidazole<br />
[[3dam]], [[3dan]], [[3dbm]] – CYP74A2 – ''Parthenium argentatum''<br />
[[2rch]], [[3dsi]] – AtCYP74A+13(S)-HOD – ''Arabidopsis thaliana''<br />
[[3dsj]] - AtCYP74A (mutant)+13(S)-HOD<br />
[[2rcl]] - AtCYP74A+vernolic acid<br />
[[3dsk]] - AtCYP74A (mutant)+ vernolic acid<br />
[[2rcm]], [[3cli]] - AtCYP74A<br />
[[2rfb]] – PtCYP – ''Picrophilus torridus''<br />
[[2rfc]] – PtCYP+phenylimidazole
[[2nz5]], [[2nza]], [[2dkk]] – ScCYP158A1 – ''Streptomyces coelicolor''<br />
[[1gwi]] - ScCYP154C1<br />
[[1wiy]] – TtCYP – ''Thermus thermophilus''<br />
[[1n97]] – TtCYP175A1

Latest revision as of 11:03, 6 January 2025

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

Drag the structure with the mouse to rotate

References

Proteopedia Page Contributors and Editors (what is this?)

Alexander Berchansky, Joel L. Sussman, Michal Harel

Retrieved from "https://proteopedia.org/index.php?title=Cytochrome_P450&oldid=4293305"