Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T06455 | Target Info | |||
| Target Name | Cytochrome P450 2A6 (CYP2A6) | ||||
| Synonyms | Cytochrome P450(I); Cytochrome P450 IIA3; Coumarin 7-hydroxylase; CYPIIA6; CYP2A6; CYP2A3 | ||||
| Target Type | Successful Target | ||||
| Gene Name | CYP2A6 | ||||
| Biochemical Class | Paired donor oxygen oxidoreductase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Methoxsalen | Ligand Info | |||||
| Structure Description | Crystal Structure of Human Microsomal P450 2A6 with Methoxsalen Bound | PDB:1Z11 | ||||
| Method | X-ray diffraction | Resolution | 2.05 Å | Mutation | No | [1] |
| PDB Sequence |
KGKLPPGPTP
39 LPFIGNYLQL49 NTEQMYNSLM59 KISERYGPVF69 TIHLGPRRVV79 VLCGHDAVRE 89 ALVDQAEEFS99 GRGEQATFDW109 VFKGYGVVFS119 NGERAKQLRR129 FSIATLRDFG 139 VGKRGIEERI149 QEEAGFLIDA159 LRGTGGANID169 PTFFLSRTVS179 NVISSIVFGD 189 RFDYKDKEFL199 SLLRMMLGIF209 QFTSTSTGQL219 YEMFSSVMKH229 LPGPQQQAFQ 239 LLQGLEDFIA249 KKVEHNQRTL259 DPNSPRDFID269 SFLIRMQEEE279 KNPNTEFYLK 289 NLVMTTLNLF299 IGGTETVSTT309 LRYGFLLLMK319 HPEVEAKVHE329 EIDRVIGKNR 339 QPKFEDRAKM349 PYMEAVIHEI359 QRFGDVIPMS369 LARRVKKDTK379 FRDFFLPKGT 389 EVYPMLGSVL399 RDPSFFSNPQ409 DFNPQHFLNE419 KGQFKKSDAF429 VPFSIGKRNC 439 FGEGLARMEL449 FLFFTTVMQN459 FRLKSSQSPK469 DIDVSPKHVG479 FATIPRNYTM 489 SFLPRHH
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| Ligand Name: Pilocarpine | Ligand Info | |||||
| Structure Description | Human Cytochrome P450 2A6 I208S/I300F/G301A/S369G in complex with Pilocarpine | PDB:3T3Q | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | Yes | [2] |
| PDB Sequence |
KLPPGPTPLP
41 FIGNYLQLNT51 EQMYNSLMKI61 SERYGPVFTI71 HLGPRRVVVL81 CGHDAVREAL 91 VDQAEEFSGR101 GEQATFDWVF111 KGYGVVFSNG121 ERAKQLRRFS131 IATLRDFGVG 141 KRGIEERIQE151 EAGFLIDALR161 GTGGANIDPT171 FFLSRTVSNV181 ISSIVFGDRF 191 DYKDKEFLSL201 LRMMLGSFQF211 TSTSTGQLYE221 MFSSVMKHLP231 GPQQQAFQLL 241 QGLEDFIAKK251 VEHNQRTLDP261 NSPRDFIDSF271 LIRMQEEEKN281 PNTEFYLKNL 291 VMTTLNLFFA301 GTETVSTTLR311 YGFLLLMKHP321 EVEAKVHEEI331 DRVIGKNRQP 341 KFEDRAKMPY351 MEAVIHEIQR361 FGDVIPMGLA371 RRVKKDTKFR381 DFFLPKGTEV 391 YPMLGSVLRD401 PSFFSNPQDF411 NPQHFLNEKG421 QFKKSDAFVP431 FSIGKRNCFG 441 EGLARMELFL451 FFTTVMQNFR461 LKSSQSPKDI471 DVSPKHVGFA481 TIPRNYTMSF 491 LPR
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Nicotine | Ligand Info | |||||
| Structure Description | Human Cytochrome P450 2A6 in complex with nicotine | PDB:4EJJ | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [3] |
| PDB Sequence |
KGKLPPGPTP
39 LPFIGNYLQL49 NTEQMYNSLM59 KISERYGPVF69 TIHLGPRRVV79 VLCGHDAVRE 89 ALVDQAEEFS99 GRGEQATFDW109 VFKGYGVVFS119 NGERAKQLRR129 FSIATLRDFG 139 VGKRGIEERI149 QEEAGFLIDA159 LRGTGGANID169 PTFFLSRTVS179 NVISSIVFGD 189 RFDYKDKEFL199 SLLRMMLGIF209 QFTSTSTGQL219 YEMFSSVMKH229 LPGPQQQAFQ 239 LLQGLEDFIA249 KKVEHNQRTL259 DPNSPRDFID269 SFLIRMQEEE279 KNPNTEFYLK 289 NLVMTTLNLF299 IGGTETVSTT309 LRYGFLLLMK319 HPEVEAKVHE329 EIDRVIGKNR 339 QPKFEDRAKM349 PYMEAVIHEI359 QRFGDVIPMS369 LARRVKKDTK379 FRDFFLPKGT 389 EVYPMLGSVL399 RDPSFFSNPQ409 DFNPQHFLNE419 KGQFKKSDAF429 VPFSIGKRNC 439 FGEGLARMEL449 FLFFTTVMQN459 FRLKSSQSPK469 DIDVSPKHVG479 FATIPRNYTM 489 SFLPR
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NCT or .NCT2 or .NCT3 or :3NCT;style chemicals stick;color identity;select .A:107 or .A:111 or .A:117 or .A:118 or .A:209 or .A:297 or .A:300 or .A:301 or .A:305 or .A:366 or .A:370 or .A:439 or .A:480; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: Coumarin | Ligand Info | |||||
| Structure Description | Crystal Structure of Human Microsomal P450 2A6 with Coumarin Bound | PDB:1Z10 | ||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [1] |
| PDB Sequence |
KGKLPPGPTP
39 LPFIGNYLQL49 NTEQMYNSLM59 KISERYGPVF69 TIHLGPRRVV79 VLCGHDAVRE 89 ALVDQAEEFS99 GRGEQATFDW109 VFKGYGVVFS119 NGERAKQLRR129 FSIATLRDFG 139 VGKRGIEERI149 QEEAGFLIDA159 LRGTGGANID169 PTFFLSRTVS179 NVISSIVFGD 189 RFDYKDKEFL199 SLLRMMLGIF209 QFTSTSTGQL219 YEMFSSVMKH229 LPGPQQQAFQ 239 LLQGLEDFIA249 KKVEHNQRTL259 DPNSPRDFID269 SFLIRMQEEE279 KNPNTEFYLK 289 NLVMTTLNLF299 IGGTETVSTT309 LRYGFLLLMK319 HPEVEAKVHE329 EIDRVIGKNR 339 QPKFEDRAKM349 PYMEAVIHEI359 QRFGDVIPMS369 LARRVKKDTK379 FRDFFLPKGT 389 EVYPMLGSVL399 RDPSFFSNPQ409 DFNPQHFLNE419 KGQFKKSDAF429 VPFSIGKRNC 439 FGEGLARMEL449 FLFFTTVMQN459 FRLKSSQSPK469 DIDVSPKHVG479 FATIPRNYTM 489 SFLPR
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .COU or .COU2 or .COU3 or :3COU;style chemicals stick;color identity;select .A:107 or .A:111 or .A:117 or .A:118 or .A:209 or .A:296 or .A:297 or .A:300 or .A:301 or .A:305 or .A:366 or .A:480; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: (5-(pyridin-3-yl)furan-2-yl)methanamine | Ligand Info | |||||
| Structure Description | Crystal Structure Of Human Microsomal P450 2A6 with the inhibitor (5-(Pyridin-3-yl)furan-2-yl)methanamine bound | PDB:2FDW | ||||
| Method | X-ray diffraction | Resolution | 2.05 Å | Mutation | No | [4] |
| PDB Sequence |
KGKLPPGPTP
39 LPFIGNYLQL49 NTEQMYNSLM59 KISERYGPVF69 TIHLGPRRVV79 VLCGHDAVRE 89 ALVDQAEEFS99 GRGEQATFDW109 VFKGYGVVFS119 NGERAKQLRR129 FSIATLRDFG 139 VGKRGIEERI149 QEEAGFLIDA159 LRGTGGANID169 PTFFLSRTVS179 NVISSIVFGD 189 RFDYKDKEFL199 SLLRMMLGIF209 QFTSTSTGQL219 YEMFSSVMKH229 LPGPQQQAFQ 239 LLQGLEDFIA249 KKVEHNQRTL259 DPNSPRDFID269 SFLIRMQEEE279 KNPNTEFYLK 289 NLVMTTLNLF299 IGGTETVSTT309 LRYGFLLLMK319 HPEVEAKVHE329 EIDRVIGKNR 339 QPKFEDRAKM349 PYMEAVIHEI359 QRFGDVIPMS369 LARRVKKDTK379 FRDFFLPKGT 389 EVYPMLGSVL399 RDPSFFSNPQ409 DFNPQHFLNE419 KGQFKKSDAF429 VPFSIGKRNC 439 FGEGLARMEL449 FLFFTTVMQN459 FRLKSSQSPK469 DIDVSPKHVG479 FATIPRNYTM 489 SFLPR
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .D3G or .D3G2 or .D3G3 or :3D3G;style chemicals stick;color identity;select .A:107 or .A:111 or .A:117 or .A:118 or .A:209 or .A:296 or .A:297 or .A:300 or .A:301 or .A:305 or .A:366 or .A:370 or .A:439 or .A:480; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: Phenacetin | Ligand Info | |||||
| Structure Description | Human Cytochrome P450 2A6 I208S/I300F/G301A/S369G in complex with Phenacetin | PDB:3EBS | ||||
| Method | X-ray diffraction | Resolution | 2.15 Å | Mutation | Yes | [5] |
| PDB Sequence |
KGKLPPGPTP
39 LPFIGNYLQL49 NTEQMYNSLM59 KISERYGPVF69 TIHLGPRRVV79 VLCGHDAVRE 89 ALVDQAEEFS99 GRGEQATFDW109 VFKGYGVVFS119 NGERAKQLRR129 FSIATLRDFG 139 VGKRGIEERI149 QEEAGFLIDA159 LRGTGGANID169 PTFFLSRTVS179 NVISSIVFGD 189 RFDYKDKEFL199 SLLRMMLGSF209 QFTSTSTGQL219 YEMFSSVMKH229 LPGPQQQAFQ 239 LLQGLEDFIA249 KKVEHNQRTL259 DPNSPRDFID269 SFLIRMQEEE279 KNPNTEFYLK 289 NLVMTTLNLF299 FAGTETVSTT309 LRYGFLLLMK319 HPEVEAKVHE329 EIDRVIGKNR 339 QPKFEDRAKM349 PYMEAVIHEI359 QRFGDVIPMG369 LARRVKKDTK379 FRDFFLPKGT 389 EVYPMLGSVL399 RDPSFFSNPQ409 DFNPQHFLNE419 KGQFKKSDAF429 VPFSIGKRNC 439 FGEGLARMEL449 FLFFTTVMQN459 FRLKSSQSPK469 DIDVSPKHVG479 FATIPRNYTM 489 SFLPR
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .N4E or .N4E2 or .N4E3 or :3N4E;style chemicals stick;color identity;select .A:107 or .A:111 or .A:117 or .A:118 or .A:209 or .A:241 or .A:296 or .A:297 or .A:300 or .A:301 or .A:305 or .A:366 or .A:369 or .A:370 or .A:480; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: N-methyl(5-(pyridin-3-yl)furan-2-yl)methanamine | Ligand Info | |||||
| Structure Description | Microsomal P450 2A6 with the inhibitor N-Methyl(5-(pyridin-3-yl)furan-2-yl)methanamine bound | PDB:2FDV | ||||
| Method | X-ray diffraction | Resolution | 1.65 Å | Mutation | No | [4] |
| PDB Sequence |
KGKLPPGPTP
39 LPFIGNYLQL49 NTEQMYNSLM59 KISERYGPVF69 TIHLGPRRVV79 VLCGHDAVRE 89 ALVDQAEEFS99 GRGEQATFDW109 VFKGYGVVFS119 NGERAKQLRR129 FSIATLRDFG 139 VGKRGIEERI149 QEEAGFLIDA159 LRGTGGANID169 PTFFLSRTVS179 NVISSIVFGD 189 RFDYKDKEFL199 SLLRMMLGIF209 QFTSTSTGQL219 YEMFSSVMKH229 LPGPQQQAFQ 239 LLQGLEDFIA249 KKVEHNQRTL259 DPNSPRDFID269 SFLIRMQEEE279 KNPNTEFYLK 289 NLVMTTLNLF299 IGGTETVSTT309 LRYGFLLLMK319 HPEVEAKVHE329 EIDRVIGKNR 339 QPKFEDRAKM349 PYMEAVIHEI359 QRFGDVIPMS369 LARRVKKDTK379 FRDFFLPKGT 389 EVYPMLGSVL399 RDPSFFSNPQ409 DFNPQHFLNE419 KGQFKKSDAF429 VPFSIGKRNC 439 FGEGLARMEL449 FLFFTTVMQN459 FRLKSSQSPK469 DIDVSPKHVG479 FATIPRNYTM 489 SFLPR
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .D2G or .D2G2 or .D2G3 or :3D2G;style chemicals stick;color identity;select .A:107 or .A:111 or .A:117 or .A:118 or .A:209 or .A:296 or .A:297 or .A:300 or .A:301 or .A:305 or .A:366 or .A:370 or .A:439 or .A:480; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: N,N-dimethyl(5-(pyridin-3-yl)furan-2-yl)methanamine | Ligand Info | |||||
| Structure Description | Microsomal P450 2A6 with the inhibitor N,N-Dimethyl(5-(pyridin-3-yl)furan-2-yl)methanamine bound | PDB:2FDU | ||||
| Method | X-ray diffraction | Resolution | 1.85 Å | Mutation | No | [4] |
| PDB Sequence |
KGKLPPGPTP
39 LPFIGNYLQL49 NTEQMYNSLM59 KISERYGPVF69 TIHLGPRRVV79 VLCGHDAVRE 89 ALVDQAEEFS99 GRGEQATFDW109 VFKGYGVVFS119 NGERAKQLRR129 FSIATLRDFG 139 VGKRGIEERI149 QEEAGFLIDA159 LRGTGGANID169 PTFFLSRTVS179 NVISSIVFGD 189 RFDYKDKEFL199 SLLRMMLGIF209 QFTSTSTGQL219 YEMFSSVMKH229 LPGPQQQAFQ 239 LLQGLEDFIA249 KKVEHNQRTL259 DPNSPRDFID269 SFLIRMQEEE279 KNPNTEFYLK 289 NLVMTTLNLF299 IGGTETVSTT309 LRYGFLLLMK319 HPEVEAKVHE329 EIDRVIGKNR 339 QPKFEDRAKM349 PYMEAVIHEI359 QRFGDVIPMS369 LARRVKKDTK379 FRDFFLPKGT 389 EVYPMLGSVL399 RDPSFFSNPQ409 DFNPQHFLNE419 KGQFKKSDAF429 VPFSIGKRNC 439 FGEGLARMEL449 FLFFTTVMQN459 FRLKSSQSPK469 DIDVSPKHVG479 FATIPRNYTM 489 SFLPR
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .D1G or .D1G2 or .D1G3 or :3D1G;style chemicals stick;color identity;select .A:107 or .A:111 or .A:117 or .A:118 or .A:209 or .A:296 or .A:297 or .A:300 or .A:301 or .A:302 or .A:305 or .A:366 or .A:370 or .A:439 or .A:480; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 4,4'-Dipyridyl disulfide | Ligand Info | |||||
| Structure Description | Microsomal P450 2A6 with the inhibitor Adrithiol bound | PDB:2FDY | ||||
| Method | X-ray diffraction | Resolution | 1.95 Å | Mutation | No | [4] |
| PDB Sequence |
KGKLPPGPTP
39 LPFIGNYLQL49 NTEQMYNSLM59 KISERYGPVF69 TIHLGPRRVV79 VLCGHDAVRE 89 ALVDQAEEFS99 GRGEQATFDW109 VFKGYGVVFS119 NGERAKQLRR129 FSIATLRDFG 139 VGKRGIEERI149 QEEAGFLIDA159 LRGTGGANID169 PTFFLSRTVS179 NVISSIVFGD 189 RFDYKDKEFL199 SLLRMMLGIF209 QFTSTSTGQL219 YEMFSSVMKH229 LPGPQQQAFQ 239 LLQGLEDFIA249 KKVEHNQRTL259 DPNSPRDFID269 SFLIRMQEEE279 KNPNTEFYLK 289 NLVMTTLNLF299 IGGTETVSTT309 LRYGFLLLMK319 HPEVEAKVHE329 EIDRVIGKNR 339 QPKFEDRAKM349 PYMEAVIHEI359 QRFGDVIPMS369 LARRVKKDTK379 FRDFFLPKGT 389 EVYPMLGSVL399 RDPSFFSNPQ409 DFNPQHFLNE419 KGQFKKSDAF429 VPFSIGKRNC 439 FGEGLARMEL449 FLFFTTVMQN459 FRLKSSQSPK469 DIDVSPKHVG479 FATIPRNYTM 489 SFLPR
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .D4G or .D4G2 or .D4G3 or :3D4G;style chemicals stick;color identity;select .A:107 or .A:111 or .A:117 or .A:118 or .A:209 or .A:296 or .A:297 or .A:300 or .A:301 or .A:305 or .A:366 or .A:370 or .A:439 or .A:480; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: Sabinene | Ligand Info | |||||
| Structure Description | Crystal structure of a cytochrome P450 2A6 in complex with a monoterpene - sabinene. | PDB:4RUI | ||||
| Method | X-ray diffraction | Resolution | 2.61 Å | Mutation | Yes | [6] |
| PDB Sequence |
GKLPPGPTPL
40 PFIGNYLQLN50 TEQMYNSLMK60 ISERYGPVFT70 IHLGPRRVVV80 LCGHDAVREA 90 LVDQAEEFSG100 RGEQATFDWV110 FKGYGVVFSN120 GERAKQLRRF130 SIATLRDFGV 140 GKRGIEERIQ150 EEAGFLIDAL160 RGTGGANIDP170 TFFLSRTVSN180 VISSIVFGDR 190 FDYKDKEFLS200 LLRMMLGIFQ210 FTSTSTGQLY220 EMFSSVMKHL230 PGPQQQAFQL 240 LQGLEDFIAK250 KVEHNQRTLD260 PNSPRDFIDS270 FLIRMQEEEK280 NPNTEFYLKN 290 LVMTTLNLFI300 GGTETVSTTL310 RYGFLLLMKH320 PEVEAKVHEE330 IDRVIGKNRQ 340 PKFEDRAKMP350 YMEAVIHEIQ360 RFGDVIPMSL370 ARRVKKDTKF380 RDFFLPKGTE 390 VYPMLGSVLR400 DPSFFSNPQD410 FNPQHFLNEK420 GQFKKSDAFV430 PFSIGKRNCF 440 GEGLARMELF450 LFFTTVMQNF460 RLKSSQSPKD470 IDVSPKHVGF480 ATIPRNYTMS 490 FLPRH
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SNE or .SNE2 or .SNE3 or :3SNE;style chemicals stick;color identity;select .D:107 or .D:111 or .D:117 or .D:118 or .D:209 or .D:297 or .D:300 or .D:301 or .D:305 or .D:366 or .D:370 or .D:480; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen. Nat Struct Mol Biol. 2005 Sep;12(9):822-3. | ||||
| REF 2 | Structural comparison of cytochromes P450 2A6, 2A13, and 2E1 with pilocarpine. FEBS J. 2012 May;279(9):1621-31. | ||||
| REF 3 | Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone binding and access channel in human cytochrome P450 2A6 and 2A13 enzymes. J Biol Chem. 2012 Aug 3;287(32):26576-85. | ||||
| REF 4 | Synthetic inhibitors of cytochrome P-450 2A6: inhibitory activity, difference spectra, mechanism of inhibition, and protein cocrystallization. J Med Chem. 2006 Nov 30;49(24):6987-7001. | ||||
| REF 5 | Key residues controlling phenacetin metabolism by human cytochrome P450 2A enzymes. Drug Metab Dispos. 2008 Dec;36(12):2582-90. | ||||
| REF 6 | Structural and biophysical characterization of human cytochromes P450 2B6 and 2A6 bound to volatile hydrocarbons: analysis and comparison. Mol Pharmacol. 2015 Apr;87(4):649-59. | ||||
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