Target Binding Site Detail

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Target General Information
Ligand General Information
Drug Binding Sites of Target
References
Target General Information  Top
Target ID T19244 Target Info
Target Name S-mephenytoin 4-hydroxylase (CYP2C9)
Synonyms Cytochrome P450 PB-1; Cytochrome P450 MP-8; Cytochrome P450 MP-4; Cytochrome P450 2C9; Cytochrome P-450MP; Cholesterol 25-hydroxylase; CYPIIC9; CYP2C10; (S)-limonene 7-monooxygenase; (S)-limonene 6-monooxygenase; (R)-limonene 6-monooxygenase
Target Type Successful Target
Gene Name CYP2C9
Biochemical Class Paired donor oxygen oxidoreductase
UniProt ID
CP2C9_HUMAN
Ligand General Information  Top
Ligand Name Losartan Ligand Info
Canonical SMILES CCCCC1=NC(=C(N1CC2=CC=C(C=C2)C3=CC=CC=C3C4=NNN=N4)CO)Cl
InChI 1S/C22H23ClN6O/c1-2-3-8-20-24-21(23)19(14-30)29(20)13-15-9-11-16(12-10-15)17-6-4-5-7-18(17)22-25-27-28-26-22/h4-7,9-12,30H,2-3,8,13-14H2,1H3,(H,25,26,27,28)
InChIKey PSIFNNKUMBGKDQ-UHFFFAOYSA-N
PubChem Compound ID 3961
Drug Binding Sites of Target  Top
PDB ID: 5X23      Crystal structure of CYP2C9 genetic variant A477T (*30) in complex with multiple losartan molecules
Method X-ray diffraction Resolution 2.00 Å Mutation Yes [1]
PDB Sequence
KLPPGPTPLP
37
VIGNILQIGI
47
KDISKSLTNL
57
SKVYGPVFTL
67
YFGLKPIVVL
77

HGYEAVKEAL
87
IDLGEEFSGR
97
GIFPLAERAN
107
RGFGIVFSNG
117
KKWKEIRRFS
127

LMTLRNFGMG
137
KRSIEDRVQE
147
EARCLVEELR
157
KTKASPCDPT
167
FILGCAPCNV
177

ICSIIFHKRF
187
DYKDQQFLNL
197
MEKLNENIKI
207
LSSPWIQICN
217
NFSPIIDYFP
227

GTHNKLLKNV
237
AFMKSYILEK
247
VKEHQESMDM
257
NNPQDFIDCF
267
LMKMEKEKHN
277

QPSEFTIESL
287
ENTAVDLFGA
297
GTETTSTTLR
307
YALLLLLKHP
317
EVTAKVQEEI
327

ERVIGRNRSP
337
CMQDRSHMPY
347
TDAVVHEVQR
357
YIDLLPTSLP
367
HAVTCDIKFR
377

NYLIPKGTTI
387
LISLTSVLHD
397
NKEFPNPEMF
407
DPHHFLDEGG
417
NFKKSKYFMP
427

FSAGKRICVG
437
EALAGMELFL
447
FLTSILQNFN
457
LKSLVDPKNL
467
DTTPVVNGFT
477

SVPPFYQLCF
487
IPI
Residue
Distance (Å)
PHE69
3.824
ILE74
4.556
GLY98
4.833
ILE99
4.940
PHE100
3.539
LEU102
4.151
ALA103
3.842
ALA106
3.591
ASN107
4.640
ARG108
2.147
VAL113
3.843
PHE114
3.982
LYS200
4.301
LEU201
2.739
ASN204
3.174
ILE205
4.170
LEU208
3.668
ILE213
4.795
GLN214
2.791
ILE215
4.861
ASN218
2.371
TYR225
4.225
PHE226
3.368
PRO227
3.410
Residue
Distance (Å)
GLY228
3.012
THR229
3.079
ASN231
3.436
LYS232
3.188
LEU233
4.046
LYS235
4.554
ASN236
3.530
VAL237
3.614
MET240
2.957
VAL292
3.689
ASP293
3.180
GLY296
3.580
ALA297
3.412
THR301
4.717
LEU361
4.658
LEU362
3.774
PRO363
3.078
THR364
2.867
SER365
2.214
LEU366
3.840
PRO367
3.324
LEU388
4.091
PHE476
2.286
THR477
4.255
PDB ID: 7RL2      Crystal Structure of the Human Cytochrome P450 2C9*8 (CYP2C9*8) Genetic Variant in Complex with the Drug Losartan
Method X-ray diffraction Resolution 2.23 Å Mutation Yes [2]
PDB Sequence
KLPPGPTPLP
37
VIGNILQIGI
47
KDISKSLTNL
57
SKVYGPVFTL
67
YFGLKPIVVL
77

HGYEAVKEAL
87
IDLGEEFSGR
97
GIFPLAERAN
107
RGFGIVFSNG
117
KKWKEIRRFS
127

LMTLRNFGMG
137
KRSIEDRVQE
147
EAHCLVEELR
157
KTKASPCDPT
167
FILGCAPCNV
177

ICSIIFHKRF
187
DYKDQQFLNL
197
MEKLNENIKI
207
LSSPWIQICN
217
NFSPIIDYFP
227

GTHNKLLKNV
237
AFMKSYILEK
247
VKEHQESMDM
257
NNPQDFIDCF
267
LMKMEKEKHN
277

QPSEFTIESL
287
ENTAVDLFGA
297
GTETTSTTLR
307
YALLLLLKHP
317
EVTAKVQEEI
327

ERVIGRNRSP
337
CMQDRSHMPY
347
TDAVVHEVQR
357
YIDLLPTSLP
367
HAVTCDIKFR
377

NYLIPKGTTI
387
LISLTSVLHD
397
NKEFPNPEMF
407
DPHHFLDEGG
417
NFKKSKYFMP
427

FSAGKRICVG
437
EALAGMELFL
447
FLTSILQNFN
457
LKSLVDPKNL
467
DTTPVVNGFA
477

SVPPFYQLCF
487
IPI
Residue
Distance (Å)
ALA106
4.008
ASN107
4.868
ARG108
2.413
VAL113
3.809
PHE114
3.906
LYS200
4.220
LEU201
3.139
ASN204
2.738
ILE205
3.910
LEU208
3.507
GLN214
3.852
TYR225
4.100
PHE226
3.432
PRO227
3.557
GLY228
3.210
Residue
Distance (Å)
THR229
3.079
ASN231
3.518
LYS232
3.189
LEU233
3.772
ASN236
3.601
VAL237
3.342
MET240
3.608
VAL292
3.430
ASP293
3.310
GLY296
3.765
ALA297
3.529
THR301
4.734
LEU362
4.059
LEU366
3.955
PDB ID: 5X24      Crystal structure of CYP2C9 genetic variant I359L (*3) in complex with multiple losartan molecules
Method X-ray diffraction Resolution 2.48 Å Mutation Yes [1]
PDB Sequence
KLPPGPTPLP
37
VIGNILQIGI
47
KDISKSLTNL
57
SKVYGPVFTL
67
YFGLKPIVVL
77

HGYEAVKEAL
87
IDLGEEFSGR
97
GIFPLAERAN
107
RGFGIVFSNG
117
KKWKEIRRFS
127

LMTLRNFGMG
137
KRSIEDRVQE
147
EARCLVEELR
157
KTKASPCDPT
167
FILGCAPCNV
177

ICSIIFHKRF
187
DYKDQQFLNL
197
MEKLNENIKI
207
LSSPWIQICN
217
NFSPIIDYFP
227

GTHNKLLKNV
237
AFMKSYILEK
247
VKEHQESMDM
257
NNPQDFIDCF
267
LMKMEKEKHN
277

QPSEFTIESL
287
ENTAVDLFGA
297
GTETTSTTLR
307
YALLLLLKHP
317
EVTAKVQEEI
327

ERVIGRNRSP
337
CMQDRSHMPY
347
TDAVVHEVQR
357
YLDLLPTSLP
367
HAVTCDIKFR
377

NYLIPKGTTI
387
LISLTSVLHD
397
NKEFPNPEMF
407
DPHHFLDEGG
417
NFKKSKYFMP
427

FSAGKRICVG
437
EALAGMELFL
447
FLTSILQNFN
457
LKSLVDPKNL
467
DTTPVVNGFA
477

SVPPFYQLCF
487
IPI
Residue
Distance (Å)
ALA106
3.930
ASN107
4.917
ARG108
2.223
VAL113
4.231
PHE114
3.613
LYS200
4.272
LEU201
4.018
ASN204
3.022
ILE205
4.688
LEU208
4.079
GLN214
4.062
TYR225
4.112
PHE226
3.170
PRO227
3.098
GLY228
2.872
THR229
2.892
Residue
Distance (Å)
ASN231
3.307
LYS232
3.192
LEU233
3.948
LYS235
4.185
ASN236
4.034
VAL237
3.467
MET240
3.680
VAL292
3.806
ASP293
3.664
GLY296
3.603
ALA297
4.061
GLU300
3.475
THR301
3.394
LEU362
4.968
LEU366
3.502
PHE476
4.097
PDB ID: 6VLT      Crystal Structure of Human P450 2C9*2 Genetic Variant in Complex with Losartan
Method X-ray diffraction Resolution 3.12 Å Mutation Yes [3]
PDB Sequence
KLPPGPTPLP
37
VIGNILQIGI
47
KDISKSLTNL
57
SKVYGPVFTL
67
YFGLKPIVVL
77

HGYEAVKEAL
87
IDLGEEFSGR
97
GIFPLAERAN
107
RGFGIVFSNG
117
KKWKEIRRFS
127

LMTLRNFGMR
139
SIEDCVQEEA
149
RCLVEELRKT
159
KASPCDPTFI
169
LGCAPCNVIC
179

SIIFHKRFDY
189
KDQQFLNLME
199
KLNENIKILS
209
SPWIQICNNF
219
SPIIDYFPGT
229

HNKLLKNVAF
239
MKSYILEKVK
249
EHQESMDMNN
259
PQDFIDCFLM
269
KMEKEKHNQP
279

SEFTIESLEN
289
TAVDLFGAGT
299
ETTSTTLRYA
309
LLLLLKHPEV
319
TAKVQEEIER
329

VIGRNRSPCM
339
QDRSHMPYTD
349
AVVHEVQRYI
359
DLLPTSLPHA
369
VTCDIKFRNY
379

LIPKGTTILI
389
SLTSVLHDNK
399
EFPNPEMFDP
409
HHFLDEGGNF
419
KKSKYFMPFS
429

AGKRICVGEA
439
LAGMELFLFL
449
TSILQNFNLK
459
SLVDPKNLDT
469
TPVVNGFASV
479

PPFYQLCFIP
489
I
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .LSN or .LSN2 or .LSN3 or :3LSN;style chemicals stick;color identity;select .A:102 or .A:103 or .A:106 or .A:108 or .A:113 or .A:114 or .A:200 or .A:201 or .A:204 or .A:205 or .A:208 or .A:233 or .A:237 or .A:240 or .A:292 or .A:296 or .A:297 or .A:300 or .A:301 or .A:362 or .A:366 or .A:476 or .A:477; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU102
4.396
ALA103
4.018
ALA106
3.443
ARG108
2.691
VAL113
4.001
PHE114
3.793
LYS200
4.906
LEU201
3.718
ASN204
2.790
ILE205
3.080
LEU208
3.805
LEU233
3.740
Residue
Distance (Å)
VAL237
3.525
MET240
2.874
VAL292
3.333
GLY296
4.097
ALA297
3.732
GLU300
3.324
THR301
3.820
LEU362
3.711
LEU366
3.549
PHE476
3.415
ALA477
4.833
PDB ID: 5XXI      Crystal structure of CYP2C9 in complex with multiple losartan molecules
Method X-ray diffraction Resolution 2.30 Å Mutation Yes [1]
PDB Sequence
KLPPGPTPLP
37
VIGNILQIGI
47
KDISKSLTNL
57
SKVYGPVFTL
67
YFGLKPIVVL
77

HGYEAVKEAL
87
IDLGEEFSGR
97
GIFPLAERAN
107
RGFGIVFSNG
117
KKWKEIRRFS
127

LMTLRNFGMG
137
KRSIEDRVQE
147
EARCLVEELR
157
KTKASPCDPT
167
FILGCAPCNV
177

ICSIIFHKRF
187
DYKDQQFLNL
197
MEKLNENIKI
207
LSSPWIQICN
217
NFSPIIDYFP
227

GTHNKLLKNV
237
AFMKSYILEK
247
VKEHQESMDM
257
NNPQDFIDCF
267
LMKMEKEKHN
277

QPSEFTIESL
287
ENTAVDLFGA
297
GTETTSTTLR
307
YALLLLLKHP
317
EVTAKVQEEI
327

ERVIGRNRSP
337
CMQDRSHMPY
347
TDAVVHEVQR
357
YIDLLPTSLP
367
HAVTCDIKFR
377

NYLIPKGTTI
387
LISLTSVLHD
397
NKEFPNPEMF
407
DPHHFLDEGG
417
NFKKSKYFMP
427

FSAGKRICVG
437
EALAGMELFL
447
FLTSILQNFN
457
LKSLVDPKNL
467
DTTPVVNGFA
477

SVPPFYQLCF
487
IPI
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .LSN or .LSN2 or .LSN3 or :3LSN;style chemicals stick;color identity;select .A:69 or .A:74 or .A:98 or .A:99 or .A:100 or .A:102 or .A:103 or .A:106 or .A:108 or .A:113 or .A:114 or .A:200 or .A:201 or .A:204 or .A:205 or .A:208 or .A:213 or .A:214 or .A:215 or .A:218 or .A:225 or .A:226 or .A:227 or .A:228 or .A:229 or .A:231 or .A:232 or .A:233 or .A:235 or .A:236 or .A:237 or .A:240 or .A:292 or .A:293 or .A:296 or .A:297 or .A:301 or .A:361 or .A:362 or .A:363 or .A:364 or .A:365 or .A:366 or .A:367 or .A:388 or .A:476 or .A:477; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
PHE69
4.365
ILE74
4.838
GLY98
4.327
ILE99
4.918
PHE100
3.549
LEU102
4.204
ALA103
4.063
ALA106
3.925
ARG108
2.367
VAL113
3.610
PHE114
2.749
LYS200
4.263
LEU201
3.078
ASN204
2.794
ILE205
4.040
LEU208
3.650
ILE213
4.929
GLN214
2.052
ILE215
3.403
ASN218
2.279
TYR225
4.435
PHE226
3.362
PRO227
3.382
GLY228
2.939
Residue
Distance (Å)
THR229
3.013
ASN231
3.554
LYS232
2.934
LEU233
4.023
LYS235
3.571
ASN236
3.860
VAL237
3.493
MET240
3.361
VAL292
3.534
ASP293
3.225
GLY296
3.542
ALA297
3.336
THR301
4.750
LEU361
3.432
LEU362
3.419
PRO363
3.179
THR364
2.657
SER365
2.224
LEU366
3.862
PRO367
3.387
LEU388
4.193
PHE476
2.025
ALA477
4.085
References  Top
REF 1 Structural Basis of Single-Nucleotide Polymorphisms in Cytochrome P450 2C9. Biochemistry. 2017 Oct 17;56(41):5476-5480.
REF 2 Insights into the Genetic Variations of Human Cytochrome P450 2C9: Structural Analysis, Characterization and Comparison. Int J Mol Sci. 2021 Sep 22;22(19):10206.
REF 3 Structure of Cytochrome P450 2C9*2 in Complex with Losartan: Insights into the Effect of Genetic Polymorphism. Mol Pharmacol. 2020 Nov;98(5):529-539.

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