Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T51843 | Target Info | |||
| Target Name | Virus RNA-dependent RNA polymerase (Viru RdRP) | ||||
| Synonyms | HCV NS5B; HCV p68 | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | Viru RdRP | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: BI 201335 | Ligand Info | |||||
| Structure Description | Crystal structure of HCV NS3/NS4A protease complexed with BI 201335 | PDB:3P8N | ||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [1] |
| PDB Sequence |
APITAYSQQT
10 RGLLGCIITS20 LTGRDKNQVD30 GEVQVLSTAT40 QSFLATCVNG50 VCWTVYHGAG 60 SKTLAGPKGP70 ITQMYTNVDQ80 DLVGWPAPPG90 ARSMTPCTCG100 SSDLYLVTRH 110 ADVIPVRRRG120 DSRGSLLSPR130 PVSYLKGSSG140 GPLLCPSGHV150 VGIFRAAVCT 160 RGVAKAVDFI170 PVESMETTMR180 AS
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| Ligand Name: (2r,6s,13ar,14ar,16as)-6-{[(Cyclopentyloxy)carbonyl]amino}-14a-[(Cyclopropylsulfonyl)carbamoyl]-5,16-Dioxooctadecahydrocyclopropa[e]pyrrolo[1,2-A][1,4]diazacyclopentadecin-2-Yl 3,4-Dihydroisoquinoline-2(1h)-Carboxylate | Ligand Info | |||||
| Structure Description | NS3/NS4A protease with inhibitor | PDB:4KTC | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | Yes | [2] |
| PDB Sequence |
APITAYSQQT
10 RGLLGCIITS20 LTGRDKNQVD30 GEVQVLSTAT40 QSFLATCVNG50 VCWTVYHGAG 60 SKTLAGPKGP70 ITQMYTNVDQ80 DLVGWPAPPG90 ARSMTPCTCG100 SSDLYLVTRH 110 ADVIPVRRRG120 DSRGSLLSPR130 PVSYLKGSSG140 GPLLCPSGHV150 VGIFRAAVCT 160 RGVAKAVDFI170 PVESM
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GLN41
3.404
SER42
3.939
PHE43
3.354
VAL55
4.336
HIS57
3.159
GLY58
3.410
VAL78
4.490
ASP79
3.238
GLN80
4.332
ASP81
3.682
ARG123
4.263
VAL132
3.555
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| Ligand Name: (1S,4R,6R,9E,12E,14S,18R)-18-(7-methoxy-8-methyl-2-propan-2-yloxyquinolin-4-yl)oxy-N-(1-methylcyclopropyl)sulfonyl-14-[(1-methylpyrazole-3-carbonyl)amino]-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]nonadeca-9,12-diene-4-carboxamide | Ligand Info | |||||
| Structure Description | Crystal structure of HCV NS3/4A R155K protease complexed with compound 4 | PDB:4I33 | ||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | Yes | [3] |
| PDB Sequence |
APITAYSQQT
10 RGLLGCIITS20 LTGRDKNQVD30 GEVQVLSTAT40 QSFLATCVNG50 VCWTVYHGAG 60 SKTLAGPKGP70 ITQMYTNVDQ80 DLVGWPAPPG90 ARSMTPCTCG100 SSDLYLVTRH 110 ADVIPVRRRG120 DSRGSLLSPR130 PVSYLKGSSG140 GPLLCPSGHV150 VGIFKAAVCT 160 RGVAKAVDFI170 PVESMETTMR180 AS
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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 .1BV or .1BV2 or .1BV3 or :31BV;style chemicals stick;color identity;select .A:41 or .A:42 or .A:43 or .A:55 or .A:56 or .A:57 or .A:58 or .A:78 or .A:79 or .A:80 or .A:81 or .A:123 or .A:132 or .A:135 or .A:136 or .A:137 or .A:138 or .A:139 or .A:154 or .A:155 or .A:156 or .A:157 or .A:158 or .A:159 or .A:168; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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GLN41
3.498
SER42
3.600
PHE43
3.490
VAL55
4.650
TYR56
3.412
HIS57
3.099
GLY58
3.628
VAL78
3.292
ASP79
3.362
GLN80
4.545
ASP81
3.468
ARG123
4.700
VAL132
4.000
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: N-(Tert-Butoxycarbonyl)-L-Alpha-Glutamyl-N-[(1r)-1-(Carboxycarbonyl)-3,3-Difluoropropyl]-L-Leucinamide | Ligand Info | |||||
| Structure Description | Inhibition of the Hepatitis C Virus NS3/4A Protease. The Crystal Structures of Two Protease-Inhibitor Complexes (inhibitor I) | PDB:1DY9 | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | Yes | [4] |
| PDB Sequence |
APITAYSQQT
10 RGLLGCIITS20 LTGRDKNQVD30 GEVQVLSTAT40 QSFLATCVNG50 VCWTVYHGAG 60 SKTLAGPKGP70 ITQMYTNVDQ80 DLVGWPAPPG90 ARSMTPCTCG100 SSDLYLVTRH 110 ADVIPVRRRG120 DSRGSLLSPR130 PVSYLKGSSG140 GPLLCPSGHV150 VGIFRAAVCT 160 RGVAKAVDFI170 PVESM
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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 .2ZF or .2ZF2 or .2ZF3 or :32ZF;style chemicals stick;color identity;select .A:42 or .A:43 or .A:55 or .A:57 or .A:81 or .A:123 or .A:132 or .A:135 or .A:136 or .A:137 or .A:138 or .A:139 or .A:154 or .A:155 or .A:156 or .A:157 or .A:158 or .A:159 or .A:168; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 3-[[(2S)-2-[[(2R)-1-[[(1R,2R)-1-carboxy-4,4-difluoro-1-hydroxybutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamoyl]-1,3-dihydroindol-2-yl]methyl]thiophene-2-carboxylic acid | Ligand Info | |||||
| Structure Description | Crystal structure of the Hepatitis C Virus NS3 Protease in complex with a peptidomimetic inhibitor | PDB:1W3C | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | Yes | [5] |
| PDB Sequence |
ITAYSQQTRG
12 LLGCIITSLT22 GRDKNQVDGE32 VQVLSTATQS42 FLATCVNGVC52 WTVYHGAGSK 62 TLAGPKGPIT72 QMYTNVDQDL82 VGWPAPPGAR92 SMTPCTCGSS102 DLYLVTRHAD 112 VIPVRRRGDS122 RGSLLSPRPV132 SYLKGSSGGP142 LLCPSGHVVG152 IFRAAVCTRG 162 VAKAVDFIPV172 ESME
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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 .DN1 or .DN12 or .DN13 or :3DN1;style chemicals stick;color identity;select .A:42 or .A:43 or .A:55 or .A:57 or .A:132 or .A:135 or .A:136 or .A:137 or .A:138 or .A:139 or .A:154 or .A:155 or .A:156 or .A:157 or .A:159; 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-[(Benzyloxy)carbonyl]-L-Isoleucyl-N-[(1r)-1-(Carboxycarbonyl)-3,3-Difluoropropyl]-L-Leucinamide | Ligand Info | |||||
| Structure Description | Inhibition of the Hepatitis C Virus NS3/4A Protease. The Crystal Structures of Two Protease-Inhibitor Complexes (inhibitor II) | PDB:1DY8 | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | Yes | [4] |
| PDB Sequence |
APITAYSQQT
10 RGLLGCIITS20 LTGRDKNQVD30 GEVQVLSTAT40 QSFLATCVNG50 VCWTVYHGAG 60 SKTLAGPKGP70 ITQMYTNVDQ80 DLVGWPAPPG90 ARSMTPCTCG100 SSDLYLVTRH 110 ADVIPVRRRG120 DSRGSLLSPR130 PVSYLKGSSG140 GPLLCPSGHV150 VGIFRAAVCT 160 RGVAKAVDFI170 PVESM
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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 .0F7 or .0F72 or .0F73 or :30F7;style chemicals stick;color identity;select .A:42 or .A:43 or .A:55 or .A:57 or .A:81 or .A:132 or .A:135 or .A:136 or .A:137 or .A:138 or .A:139 or .A:154 or .A:155 or .A:156 or .A:157 or .A:158 or .A:159 or .A:168; 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-[(Cyclopentyloxy)carbonyl]-3-Methyl-L-Valyl-(4r)-N-[(1r,2s)-1-Carboxy-2-Ethenylcyclopropyl]-4-[(7-Methoxy-2-{2-[(2-Methylpropanoyl)amino]-1,3-Thiazol-4-Yl}quinolin-4-Yl)oxy]-L-Prolinamide | Ligand Info | |||||
| Structure Description | Crystal structure of HCV NS3/NS4A protease complexed with des-bromine analogue of BI 201335 | PDB:3P8O | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [1] |
| PDB Sequence |
APITAYSQQT
10 RGLLGCIITS20 LTGRDKNQVD30 GEVQVLSTAT40 QSFLATCVNG50 VCWTVYHGAG 60 SKTLAGPKGP70 ITQMYTNVDQ80 DLVGWPAPPG90 ARSMTPCTCG100 SSDLYLVTRH 110 ADVIPVRRRG120 DSRGSLLSPR130 PVSYLKGSSG140 GPLLCPSGHV150 VGIFRAAVCT 160 RGVAKAVDFI170 PVESMETTMR180 AS
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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 .L5T or .L5T2 or .L5T3 or :3L5T;style chemicals stick;color identity;select .A:56 or .A:57 or .A:78 or .A:79 or .A:80 or .A:81 or .A:123 or .A:132 or .A:135 or .A:136 or .A:137 or .A:138 or .A:139 or .A:154 or .A:155 or .A:156 or .A:157 or .A:158 or .A:159 or .A:168; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Combined X-ray, NMR, and kinetic analyses reveal uncommon binding characteristics of the hepatitis C virus NS3-NS4A protease inhibitor BI 201335. J Biol Chem. 2011 Apr 1;286(13):11434-43. | ||||
| REF 2 | Discovery of danoprevir (ITMN-191/R7227), a highly selective and potent inhibitor of hepatitis C virus (HCV) NS3/4A protease. J Med Chem. 2014 Mar 13;57(5):1753-69. | ||||
| REF 3 | Molecular mechanism by which a potent hepatitis C virus NS3-NS4A protease inhibitor overcomes emergence of resistance. J Biol Chem. 2013 Feb 22;288(8):5673-81. | ||||
| REF 4 | Inhibition of the hepatitis C virus NS3/4A protease. The crystal structures of two protease-inhibitor complexes. J Biol Chem. 2000 Mar 10;275(10):7152-7. | ||||
| REF 5 | The design and enzyme-bound crystal structure of indoline based peptidomimetic inhibitors of hepatitis C virus NS3 protease. J Med Chem. 2004 Dec 16;47(26):6443-6. | ||||
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