Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T57392 | Target Info | |||
| Target Name | Debrisoquine 4-hydroxylase (CYP2D6) | ||||
| Synonyms | P450-DB1; Cytochrome P450-DB1; Cytochrome P450 2D6; CYPIID6; CYP2DL1 | ||||
| Target Type | Successful Target | ||||
| Gene Name | CYP2D6 | ||||
| Biochemical Class | Paired donor oxygen oxidoreductase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | 10-{2-[(2r)-1-Methylpiperidin-2-Yl]ethyl}-2-(Methylsulfanyl)-10h-Phenothiazine | Ligand Info | |||
| Canonical SMILES | CN1CCCCC1CCN2C3=CC=CC=C3SC4=C2C=C(C=C4)SC | ||||
| InChI | 1S/C21H26N2S2/c1-22-13-6-5-7-16(22)12-14-23-18-8-3-4-9-20(18)25-21-11-10-17(24-2)15-19(21)23/h3-4,8-11,15-16H,5-7,12-14H2,1-2H3/t16-/m1/s1 | ||||
| InChIKey | KLBQZWRITKRQQV-MRXNPFEDSA-N | ||||
| PubChem Compound ID | 6604030 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 3TBG Human cytochrome P450 2D6 with two thioridazines bound in active site | ||||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [1] |
| PDB Sequence |
GKLPPGPLPL
40 PGLGNLLHVD50 FQNTPYCFDQ60 LRRRFGDVFS70 LQLAWTPVVV80 LNGLAAVREA 90 LVTHGEDTAD100 RPPVPITQIL110 GFGPRSQGVF120 LARYGPAWRE130 QRRFSVSTLR 140 NLGLGKKSLE150 QWVTEEAACL160 CAAFANHSGR170 PFRPNGLLDK180 AVSNVIASLT 190 CGRRFEYDDP200 RFLRLLDLAQ210 EGLKEESGFL220 REVLNAVPVL230 LHIPALAGKV 240 LRFQKAFLTQ250 LDELLTEHRM260 TWDPAQPPRD270 LTEAFLAEME280 KAKGNPESSF 290 NDENLRIVVA300 DLFSAGMVTT310 STTLAWGLLL320 MILHPDVQRR330 VQQEIDDVIG 340 QVRRPEMGDQ350 AHMPYTTAVI360 HEVQRFGDIV370 PLGVTHMTSR380 DIEVQGFRIP 390 KGTTLITNLS400 SVLKDEAVWE410 KPFRFHPEHF420 LDAQGHFVKP430 EAFLPFSAGR 440 RACLGEPLAR450 MELFLFFTSL460 LQHFSFSVPT470 GQPRPSHHGV480 FAFLVSPSPY 490 ELCAVPR
|
|||||
|
|
PHE51
3.713
THR54
3.541
LEU73
3.850
THR76
3.377
VAL78
3.859
LEU110
3.868
PHE112
3.699
PHE120
3.574
LEU121
3.688
LEU208
4.711
ALA209
3.822
GLY212
3.477
LEU213
3.706
GLU216
3.291
SER217
3.975
GLU222
2.964
GLN244
3.570
|
|||||
| PDB ID: 6CSB V308E mutant of cytochrome P450 2D6 complexed with thioridazine | ||||||
| Method | X-ray diffraction | Resolution | 2.39 Å | Mutation | Yes | [2] |
| PDB Sequence |
KLPPGPNTPY
56 CFDQLRRRFG66 DVFSLQLAWT76 PVVVLNGLAA86 VREALVTHGE96 DTADRPPVPI 106 TQILGFGPRS116 QGVFLARYGP126 AWREQRRFSV136 STLRNLGLGK146 KSLEQWVTEE 156 AACLCAAFAN166 HSGRPFRPNG176 LLDKAVSNVI186 ASLTCGRRFE196 YDDPRFLRLL 206 DLAQEGLKEE216 SGFLREVLNA226 VPVLLHIPAL236 AGKVLRFQKA246 FLTQLDELLT 256 EHRMTWDPAQ266 PPRDLTEAFL276 AEMEKAKGNP286 ESSFNDENLR296 IVVADLFSAG 306 METTSTTLAW316 GLLLMILHPD326 VQRRVQQEID336 DVIGQVRRPE346 MGDQAHMPYT 356 TAVIHEVQRF366 GDIVPLGVTH376 MTSRDIEVQG386 FRIPKGTTLI396 TNLSSVLKDE 406 AVWEKPFRFH416 PEHFLDAQGH426 FVKPEAFLPF436 SAGRRACLGE446 PLARMELFLF 456 FTSLLQHFSF466 SVPTGQPRPS476 HHGVFAFLVS486 PSPYELCAVP496 RH |
|||||
|
|
THR54
4.260
LEU73
3.927
ALA74
3.938
THR76
3.743
VAL78
4.008
LEU110
3.939
PHE112
3.662
PHE120
3.632
LEU121
3.633
LEU208
4.703
ALA209
3.307
GLY212
3.743
LEU213
3.895
GLU216
3.271
GLU222
3.346
|
|||||
| PDB ID: 4WNW Human Cytochrome P450 2D6 Thioridazine Complex | ||||||
| Method | X-ray diffraction | Resolution | 3.30 Å | Mutation | No | [1] |
| PDB Sequence |
LPPGPLPLPG
42 LGNLLHVDFQ52 NTPYCFDQLR62 RRFGDVFSLQ72 LAWTPVVVLN82 GLAAVREALV 92 THGEDTADRP102 PVPITQILGF112 GPRSQGVFLA122 RYGPAWREQR132 RFSVSTLRNL 142 KSLEQWVTEE156 AACLCAAFAN166 HSGRPFRPNG176 LLDKAVSNVI186 ASLTCGRRFE 196 YDDPRFLRLL206 DLAQEGLKEE216 SGFLREVLNA226 VPVLLHIPAL236 AGKVLRFQKA 246 FLTQLDELLT256 EHRMTWDPAQ266 PPRDLTEAFL276 AEMEKAKGNP286 ESSFNDENLR 296 IVVADLFSAG306 MVTTSTTLAW316 GLLLMILHPD326 VQRRVQQEID336 DVIGQVRRPE 346 MGDQAHMPYT356 TAVIHEVQRF366 GDIVPLGVTH376 MTSRDIEVQG386 FRIPKGTTLI 396 TNLSSVLKDE406 AVWEKPFRFH416 PEHFLDAQGH426 FVKPEAFLPF436 SAGRRACLGE 446 PLARMELFLF456 FTSLLQHFSF466 SVPTGQPRPS476 HHGVFAFLVS486 PSPYELCAVP 496 R
|
|||||
|
|
LEU110
4.204
PHE112
3.576
PHE120
3.564
LEU121
3.707
ALA209
3.346
GLY212
3.770
LEU213
3.598
GLU216
3.560
GLN244
3.193
LEU248
4.193
ILE297
4.359
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Contributions of ionic interactions and protein dynamics to cytochrome P450 2D6 (CYP2D6) substrate and inhibitor binding. J Biol Chem. 2015 Feb 20;290(8):5092-5104. | ||||
| REF 2 | Characteristic conformational changes on the distal and proximal surfaces of cytochrome P450 2D6 in response to substrate binding | ||||
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