Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T05152 | Target Info | |||
| Target Name | Hepatitis C virus RNA-directed RNA polymerase (HCV NS5B) | ||||
| Synonyms | HCV NS5B; HCV p68 | ||||
| Target Type | Successful Target | ||||
| Gene Name | HCV NS5B | ||||
| Biochemical Class | Peptidase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: (11s)-10-[(2,5-Dimethyl-1,3-Oxazol-4-Yl)carbonyl]-11-{2-Fluoro-4-[(2-Methylprop-2-En-1-Yl)oxy]phenyl}-3,3-Dimethyl-2,3,4,5,10,11-Hexahydrothiopyrano[3,2-B][1,5]benzodiazepin-6-Ol 1,1-Dioxide | Ligand Info | |||||
| Structure Description | HCV NS5B genotype 1a in complex with 1,5 benzodiazepine inhibitor 6 | PDB:3HKW | ||||
| Method | X-ray diffraction | Resolution | 1.55 Å | Mutation | No | [1] |
| PDB Sequence |
SMSYSWTGAL
10 VTPCAAEEQK20 LPINALSNSL30 LRHHNMVYST40 TSRSACQRQK50 KVTFDRLQVL 60 DSHYQDVLKE70 VKAAASKVKA80 NLLSVEEACS90 LTPPHSARSK100 FGYGAKDVRC 110 HARKAVTHIN120 SVWKDLLEDS130 VTPIDTTIMA140 KNEVFCVQPG152 GRKPARLIVF 162 PDLGVRVCEK172 MALYDVVSKL182 PQAVMGSSYG192 FQYSPGQRVE202 FLVQAWKSKK 212 SPMGFSYDTR222 CFDSTVTESD232 IRTEEAIYQC242 CDLDPQARVA252 IKSLTERLYV 262 GGPLTNSKGE272 NCGYRRCRAS282 GVLTTSCGNT292 LTCYIKARAA302 CRAAGLQDCT 312 MLVCGDDLVV322 ICESAGVQED332 AASLRAFTEA342 MTRYSAPPGD352 PPQPEYDLEL 362 ITSCSSNVSV372 AHDGAGKRVY382 YLTRDPTTPL392 ARAAWETARH402 TPVNSWLGNI 412 IMFAPTLWAR422 MILMTHFFSV432 LIARDQLEQA442 LDCEIYGACY452 SIEPLDLPPI 462 IQRLHGLSAF472 SLHSYSPGEI482 NRVAACLRKL492 GVPPLRAWRH502 RARSVRAKLL 512 SRGGRAAICG522 KYLFNWAVRT532 KLKLTPIAAA542 GQLDLSGWFT552 AGYSGGDIYH 562 S
|
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ARG158
4.531
PHE193
3.323
PRO197
3.997
ARG200
3.702
CYS316
4.936
SER365
4.747
CYS366
3.462
SER367
2.671
SER368
3.711
LEU384
3.894
ARG386
3.517
|
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| Ligand Name: N-[(2s)-Butan-2-Yl]-6-[(3r)-3-{[4-(Trifluoromethoxy)benzyl]carbamoyl}-4-{[4-(Trifluoromethoxy)phenyl]sulfonyl}piperazin-1-Yl]pyridazine-3-Carboxamide | Ligand Info | |||||
| Structure Description | Crystal structure of the hepatitis C virus NS5B RNA-dependent RNA polymerase genotype 1a complex with N-[(2S)-butan-2-yl]-6-[(3R)-3-{[4-(trifluoromethoxy)benzyl]carbamoyl}-4-{[4-(trifluoromethoxy)phenyl]sulfonyl}piperazin-1-yl]pyridazine-3-carboxamide | PDB:3QGI | ||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | No | [2] |
| PDB Sequence |
SMSYSWTGAL
10 VTPCAAEEQK20 LPINALSNSL30 LRHHNLVYST40 TSRSACQRQK50 KVTFDRLQVL 60 DSHYQDVLKE70 VKAAASKVKA80 NLLSVEEACS90 LTPPHSAKSK100 FGYGAKDVRC 110 HARKAVAHIN120 SVWKDLLEDS130 VTPIDTTIMA140 KNEVFCVQPE150 KRKPARLIVF 162 PDLGVRVCEK172 MALYDVVSKL182 PLAVMGSSYG192 FQYSPGQRVE202 FLVQAWKSKK 212 TPMGFSYDTR222 CFDSTVTESD232 IRTEEAIYQC242 CDLDPQARVA252 IKSLTERLYV 262 GGPLTNSRGE272 NCGYRRCRAS282 GVLTTSCGNT292 LTCYIKARAA302 CRAAGLQDCT 312 MLVCGDDLVV322 ICESAGVQED332 AASLRAFTEA342 MTRYSAPPGD352 PPQPEYDLEL 362 ITSCSSNVSV372 AHDGAGKRVY382 YLTRDPTTPL392 ARAAWETARH402 TPVNSWLGNI 412 IMFAPTLWAR422 MILMTHFFSV432 LIARDQLEQA442 LNCEIYGACY452 SIEPLDLPPI 462 IQRLHGLSAF472 SLHSYSPGEI482 NRVAACLRKL492 GVPPLRAWRH502 RARSVRARLL 512 SRGGRAAICG522 KYLFNWAVRT532 KLKLTPIAAA542 GRLDLSGWFT552 AGYSGGDIYH 562 S
|
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VAL179
3.188
SER180
4.365
PRO183
4.413
TYR191
3.295
GLY192
3.638
PHE193
3.410
TYR195
2.986
SER196
3.247
PRO197
3.375
ARG200
3.651
SER288
2.807
CYS289
3.804
THR292
4.114
CYS316
4.449
CYS366
3.825
SER368
3.010
|
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| Ligand Name: N-Cyclopropyl-6-[(3r)-3-{[4-(Trifluoromethoxy)benzyl]carbamoyl}-4-{[4-(Trifluoromethoxy)phenyl]sulfonyl}piperazin-1-Yl]pyridazine-3-Carboxamide | Ligand Info | |||||
| Structure Description | Crystal structure of the hepatitis C virus NS5B RNA-dependent RNA polymerase genotype 1a complex with N-cyclopropyl-6-[(3R)-3-{[4-(trifluoromethoxy)benzyl]carbamoyl}-4-{[4-(trifluoromethoxy)phenyl]sulfonyl}piperazin-1-yl]pyridazine-3-carboxamide | PDB:3QGH | ||||
| Method | X-ray diffraction | Resolution | 2.14 Å | Mutation | No | [2] |
| PDB Sequence |
SMSYSWTGAL
10 VTPCAAEEQK20 LPINALSNSL30 LRHHNLVYST40 TSRSACQRQK50 KVTFDRLQVL 60 DSHYQDVLKE70 VKAAASKVKA80 NLLSVEEACS90 LTPPHSAKSK100 FGYGAKDVRC 110 HARKAVAHIN120 SVWKDLLEDS130 VTPIDTTIMA140 KNEVFCVQPE150 KRKPARLIVF 162 PDLGVRVCEK172 MALYDVVSKL182 PLAVMGSSYG192 FQYSPGQRVE202 FLVQAWKSKK 212 TPMGFSYDTR222 CFDSTVTESD232 IRTEEAIYQC242 CDLDPQARVA252 IKSLTERLYV 262 GGPLTNSRGE272 NCGYRRCRAS282 GVLTTSCGNT292 LTCYIKARAA302 CRAAGLQDCT 312 MLVCGDDLVV322 ICESAGVQED332 AASLRAFTEA342 MTRYSAPPGD352 PPQPEYDLEL 362 ITSCSSNVSV372 AHDGAGKRVY382 YLTRDPTTPL392 ARAAWETARH402 TPVNSWLGNI 412 IMFAPTLWAR422 MILMTHFFSV432 LIARDQLEQA442 LNCEIYGACY452 SIEPLDLPPI 462 IQRLHGLSAF472 SLHSYSPGEI482 NRVAACLRKL492 GVPPLRAWRH502 RARSVRARLL 512 SRGGRAAICG522 KYLFNWAVRT532 KLKLTPIAAA542 GRLDLSGWFT552 AGYSGGDIY |
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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 .63F or .63F2 or .63F3 or :363F;style chemicals stick;color identity;select .A:179 or .A:183 or .A:191 or .A:192 or .A:193 or .A:194 or .A:195 or .A:196 or .A:197 or .A:200 or .A:288 or .A:289 or .A:292 or .A:316 or .A:366 or .A:368 or .A:384 or .A:413 or .A:414 or .A:415 or .A:447 or .A:448 or .A:450 or .A:452 or .A:454 or .A:462 or .A:466 or .A:547 or .A:548 or .A:551 or .A:555; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
VAL179
3.356
PRO183
3.789
TYR191
2.979
GLY192
3.534
PHE193
3.444
GLN194
4.872
TYR195
2.888
SER196
3.223
PRO197
3.453
ARG200
3.674
SER288
2.982
CYS289
3.505
THR292
4.336
CYS316
4.357
CYS366
3.842
SER368
2.958
|
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| Ligand Name: 3-Benzofurancarboxamide, 6-[(7-chloro-1,3-dihydro-1-hydroxy-2,1-benzoxaborol-5-yl)(methylsulfonyl)amino]-5-cyclopropyl-2-(4-fluorophenyl)-N-methyl- | Ligand Info | |||||
| Structure Description | HCV NS5B 1A Y316 bound to Compound 49 | PDB:6MVO | ||||
| Method | X-ray diffraction | Resolution | 1.95 Å | Mutation | Yes | [3] |
| PDB Sequence |
SMSYSWTGAL
10 VTPCAAEEQK20 LPINALSNSL30 LRHHNLVYST40 TSRSACQRQK50 KVTFDRLQVL 60 DSHYQDVLKE70 VKAAASKVKA80 NLLSVEEACS90 LTPPHSAKSK100 YGYGAKDVRS 110 HASRAVAHIN120 SVWKDLLEDS130 VTPIDTTIMA140 KNEVFCVQPE150 KGGRKPARLI 160 VFPDLGVRVC170 EKMALYDVVS180 KLPLAVMGSS190 YGFQYSPGQR200 VEFLVQAWKS 210 KKTPMGFSYD220 TRCFDSTVTE230 SDIRTEEAIY240 QCCDLDPQAR250 VAIKSLTERL 260 YVGGPLTNSR270 GENCGYRRCR280 ASGVLTTSCG290 NTLTCYIKAR300 AACRAAGLQD 310 CTMLVYGDDL320 VVICESAGVQ330 EDAASLRAFT340 EAMTRYSAPP350 GDPPQPEYDL 360 ELITSCSSNV370 SVAHDGAGKR380 VYYLTRDPTT390 PLARAAWETA400 RHTPVNSWLG 410 NIIMFAPTLW420 ARMILMTHFF430 SVLIARDQLE440 QALDCEIYGA450 CYSIEPLDLP 460 PIIQRLHGLS470 AFSLHSYSPG480 EINRVAACLR490 KLGVPPLRAW500 RHRARSVRAR 510 LLSRGGRAAI520 CGKYLFNWAV530 RTKLKLTPIA540 AAGQLALSGW550 FTAGYSGGDI 560 YH
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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 .K4P or .K4P2 or .K4P3 or :3K4P;style chemicals stick;color identity;select .A:192 or .A:197 or .A:200 or .A:204 or .A:314 or .A:315 or .A:316 or .A:319 or .A:320 or .A:321 or .A:360 or .A:363 or .A:364 or .A:365 or .A:366 or .A:367 or .A:368 or .A:369 or .A:370 or .A:384 or .A:386 or .A:410 or .A:411 or .A:414 or .A:415 or .A:448; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLY192
4.811
PRO197
3.755
ARG200
3.038
LEU204
3.310
LEU314
3.353
VAL315
4.355
TYR316
3.234
ASP319
3.803
LEU320
4.408
VAL321
3.734
LEU360
4.084
ILE363
3.072
THR364
4.633
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | 1a/1b subtype profiling of nonnucleoside polymerase inhibitors of hepatitis C virus. J Virol. 2010 Mar;84(6):2923-34. | ||||
| REF 2 | Investigation of the mode of binding of a novel series of N-benzyl-4-heteroaryl-1-(phenylsulfonyl)piperazine-2-carboxamides to the hepatitis C virus polymerase. Bioorg Med Chem Lett. 2011 Apr 15;21(8):2212-5. | ||||
| REF 3 | Design of N-Benzoxaborole Benzofuran GSK8175-Optimization of Human Pharmacokinetics Inspired by Metabolites of a Failed Clinical HCV Inhibitor. J Med Chem. 2019 Apr 11;62(7):3254-3267. | ||||
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