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 | Prinomastat | Ligand Info | |||
| Canonical SMILES | CC1(C(N(CCS1)S(=O)(=O)C2=CC=C(C=C2)OC3=CC=NC=C3)C(=O)NO)C | ||||
| InChI | 1S/C18H21N3O5S2/c1-18(2)16(17(22)20-23)21(11-12-27-18)28(24,25)15-5-3-13(4-6-15)26-14-7-9-19-10-8-14/h3-10,16,23H,11-12H2,1-2H3,(H,20,22)/t16-/m0/s1 | ||||
| InChIKey | YKPYIPVDTNNYCN-INIZCTEOSA-N | ||||
| PubChem Compound ID | 466151 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 6CSD V308E mutant of cytochrome P450 2D6 complexed with prinomastat | ||||||
| Method | X-ray diffraction | Resolution | 2.39 Å | Mutation | Yes | [1] |
| PDB Sequence |
KLPPGPNLLH
48 VDFQNTPYCF58 DQLRRRFGDV68 FSLQLAWTPV78 VVLNGLAAVR88 EALVTHGEDT 98 ADRPPVPITQ108 ILGFGPRSQG118 VFLARYGPAW128 REQRRFSVST138 LRNLGLGKKS 148 LEQWVTEEAA158 CLCAAFANHS168 GRPFRPNGLL178 DKAVSNVIAS188 LTCGRRFEYD 198 DPRFLRLLDL208 AQEGLKEESG218 FLREVLNAVP228 VLLHIPALAG238 KVLRFQKAFL 248 TQLDELLTEH258 RMTWDPAQPP268 RDLTEAFLAE278 MEKAKGNPES288 SFNDENLRIV 298 VADLFSAGME308 TTSTTLAWGL318 LLMILHPDVQ328 RRVQQEIDDV338 IGQVRRPEMG 348 DQAHMPYTTA358 VIHEVQRFGD368 IVPLGVTHMT378 SRDIEVQGFR388 IPKGTTLITN 398 LSSVLKDEAV408 WEKPFRFHPE418 HFLDAQGHFV428 KPEAFLPFSA438 GRRACLGEPL 448 ARMELFLFFT458 SLLQHFSFSV468 PTGQPRPSHH478 GVFAFLVSPS488 PYELCAVPRH 498 HH
|
|||||
|
|
LEU110
4.031
PHE112
4.015
PHE120
3.425
LEU121
3.678
ALA209
4.917
GLY212
3.520
LEU213
3.767
GLU216
3.435
GLN244
3.483
PHE247
4.725
ILE297
3.811
|
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| PDB ID: 3TDA Competitive replacement of thioridazine by prinomastat in crystals of cytochrome P450 2D6 | ||||||
| Method | X-ray diffraction | Resolution | 2.67 Å | Mutation | No | [2] |
| 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
|
|||||
|
|
LEU110
3.909
PHE112
3.963
PHE120
3.309
LEU121
3.926
ALA209
4.747
GLY212
4.203
LEU213
3.970
GLU216
3.569
GLN244
3.231
PHE247
4.465
LEU248
4.644
|
|||||
| PDB ID: 3QM4 Human Cytochrome P450 (CYP) 2D6 - Prinomastat Complex | ||||||
| Method | X-ray diffraction | Resolution | 2.85 Å | Mutation | No | [3] |
| PDB Sequence |
LPPGPLPLPG
42 LGNLLHVDFQ52 NTPYCFDQLR62 RRFGDVFSLQ72 LAWTPVVVLN82 GLAAVREALV 92 THGEDTADRP102 PVPITQILGF112 GPRSQGVFLA122 RYGPAWREQR132 RFSVSTLRNL 142 GLGKKSLEQW152 VTEEAACLCA162 AFANHSGRPF172 RPNGLLDKAV182 SNVIASLTCG 192 RRFEYDDPRF202 LRLLDLAQEG212 LKEESGFLRE222 VLNAVPVLLH232 IPALAGKVLR 242 FQKAFLTQLD252 ELLTEHRMTW262 DPAQPPRDLT272 EAFLAEMEKA282 KGNPESSFND 292 ENLRIVVADL302 FSAGMVTTST312 TLAWGLLLMI322 LHPDVQRRVQ332 QEIDDVIGQV 342 RRPEMGDQAH352 MPYTTAVIHE362 VQRFGDIVPL372 GVTHMTSRDI382 EVQGFRIPKG 392 TTLITNLSSV402 LKDEAVWEKP412 FRFHPEHFLD422 AQGHFVKPEA432 FLPFSAGRRA 442 CLGEPLARME452 LFLFFTSLLQ462 HFSFSVPTGQ472 PRPSHHGVFA482 FLVSPSPYEL 492 CAVPR
|
|||||
|
|
LEU110
3.440
PHE112
4.028
PHE120
3.260
ALA209
4.594
GLY212
3.373
LEU213
3.586
GLU216
3.462
GLN244
3.019
PHE247
3.376
LEU248
3.963
ILE297
4.566
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Characteristic conformational changes on the distal and proximal surfaces of cytochrome P450 2D6 in response to substrate binding | ||||
| REF 2 | 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 3 | Crystal structure of human cytochrome P450 2D6 with prinomastat bound. J Biol Chem. 2012 Mar 30;287(14):10834-43. | ||||
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