Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T79068 | Target Info | |||
| Target Name | Bacterial Fatty acid synthetase I (Bact inhA) | ||||
| Synonyms | Enoyl-[acyl-carrier-protein] reductase [NADH]; Bacterial InhA | ||||
| Target Type | Successful Target | ||||
| Gene Name | Bact inhA | ||||
| Biochemical Class | CH-CH donor oxidoreductase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Isonicotinic-acetyl-nicotinamide-adenine dinucleotide | Ligand Info | |||
| Canonical SMILES | C1=CN=CC=C1C(=O)C2=C(C=[N+](C=C2)C3C(C(C(O3)COP(=O)([O-])OP(=O)(O)OCC4C(C(C(O4)N5C=NC6=C(N=CN=C65)N)O)O)O)O)C(=O)N | ||||
| InChI | 1S/C27H30N8O15P2/c28-23-17-25(32-10-31-23)35(11-33-17)27-22(40)20(38)16(49-27)9-47-52(44,45)50-51(42,43)46-8-15-19(37)21(39)26(48-15)34-6-3-13(14(7-34)24(29)41)18(36)12-1-4-30-5-2-12/h1-7,10-11,15-16,19-22,26-27,37-40H,8-9H2,(H5-,28,29,31,32,41,42,43,44,45)/t15-,16-,19-,20-,21-,22-,26-,27-/m1/s1 | ||||
| InChIKey | SURAWYIAXPVHGO-XDBKRARRSA-N | ||||
| PubChem Compound ID | 5289618 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 4TRO Structure of the enoyl-ACP reductase of Mycobacterium tuberculosis InhA, inhibited with the active metabolite of isoniazid | ||||||
| Method | X-ray diffraction | Resolution | 1.40 Å | Mutation | No | [1] |
| PDB Sequence |
TGLLDGKRIL
11 VSGIITDSSI21 AFHIARVAQE31 QGAQLVLTGF41 DRLRLIQRIT51 DRLPAKAPLL 61 ELDVQNEEHL71 ASLAGRVTEA81 IGAGNKLDGV91 VHSIGFMPQT101 GMGINPFFDA 111 PYADVSKGIH121 ISAYSYASMA131 KALLPIMNPG141 GSIVGMDFDP151 SRAMPAYNWM 161 TVAKSALESV171 NRFVAREAGK181 YGVRSNLVAA191 GPIRTLAMSA201 IVGGALGEEA 211 GAQIQLLEEG221 WDQRAPIGWN231 MKDATPVAKT241 VCALLSDWLP251 ATTGDIIYAD 261 GGAHTQLL
|
|||||
|
|
GLY14
2.751
ILE15
3.608
ILE16
3.506
THR17
4.932
SER19
4.951
SER20
2.707
ILE21
2.881
ALA22
4.443
PHE41
3.473
LEU63
3.545
ASP64
3.072
VAL65
3.120
GLN66
4.341
SER94
3.167
ILE95
3.388
GLY96
3.420
PHE97
4.033
|
|||||
| PDB ID: 2NV6 Mycobacterium tuberculosis InhA (S94A) bound with INH-NAD adduct | ||||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | Yes | [2] |
| PDB Sequence |
AGLLDGKRIL
11 VSGIITDSSI21 AFHIARVAQE31 QGAQLVLTGF41 DRLRLIQRIT51 DRLPAKAPLL 61 ELDVQNEEHL71 ASLAGRVTEA81 IGAGNKLDGV91 VHAIGFMPQT101 GMGINPFFDA 111 PYADVSKGIH121 ISAYSYASMA131 KALLPIMNPG141 GSIVGMDFDP151 SRAMPAYNWM 161 TVAKSALESV171 NRFVAREAGK181 YGVRSNLVAA191 GPIRTLAMSA201 IVGGALGEEA 211 GAQIQLLEEG221 WDQRAPIGWN231 MKDATPVAKT241 VCALLSDWLP251 ATTGDIIYAD 261 GGAHTQLL
|
|||||
|
|
GLY14
2.739
ILE15
3.580
ILE16
3.250
THR17
4.892
SER19
4.954
SER20
2.749
ILE21
2.898
ALA22
4.459
PHE41
3.395
LEU63
3.266
ASP64
3.062
VAL65
2.995
GLN66
4.320
ALA94
3.211
ILE95
3.268
GLY96
3.364
|
|||||
| PDB ID: 2IDZ Crystal structure of wild type Enoyl-ACP(CoA) reductase from Mycobacterium tuberculosis in complex with NADH-INH | ||||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [3] |
| PDB Sequence |
TGLLDGKRIL
11 VSGIITDSSI21 AFHIARVAQE31 QGAQLVLTGF41 DRLRLIQRIT51 DRLPAKAPLL 61 ELDVQNEEHL71 ASLAGRVTEA81 IGAGNKLDGV91 VHSIGFMPQT101 GMGINPFFDA 111 PYADVSKGIH121 ISAYSYASMA131 KALLPIMNPG141 GSIVGMDFDP151 SRAMPAYNWM 161 TVAKSALESV171 NRFVAREAGK181 YGVRSNLVAA191 GPIRTLAMSA201 IVGGALGEEA 211 GAQIQLLEEG221 WDQRAPIGWN231 MKDATPVAKT241 VCALLSDWLP251 ATTGDIIYAD 261 GGAHTQLL
|
|||||
|
|
GLY14
2.688
ILE15
3.511
ILE16
3.270
THR17
4.877
SER19
4.958
SER20
2.469
ILE21
2.805
ALA22
4.388
PHE41
3.365
LEU63
3.177
ASP64
2.977
VAL65
2.899
GLN66
4.239
SER94
3.055
ILE95
3.137
GLY96
3.361
PHE97
4.275
|
|||||
| PDB ID: 2IE0 Crystal Structure of Isoniazid-resistant I21V Enoyl-ACP(COA) Reductase Mutant Enzyme From MYCOBACTERIUM TUBERCULOSIS in Complex with NADH-INH | ||||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | Yes | [3] |
| PDB Sequence |
TGLLDGKRIL
11 VSGIITDSSV21 AFHIARVAQE31 QGAQLVLTGF41 DRLRLIQRIT51 DRLPAKAPLL 61 ELDVQNEEHL71 ASLAGRVTEA81 IGAGNKLDGV91 VHSIGFMPQT101 GMGINPFFDA 111 PYADVSKGIH121 ISAYSYASMA131 KALLPIMNPG141 GSIVGMDFDP151 SRAMPAYNWM 161 TVAKSALESV171 NRFVAREAGK181 YGVRSNLVAA191 GPIRTLAMSA201 IVGGALGEEA 211 GAQIQLLEEG221 WDQRAPIGWN231 MKDATPVAKT241 VCALLSDWLP251 ATTGDIIYAD 261 GGAHTQLL
|
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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 .ZID or .ZID2 or .ZID3 or :3ZID;style chemicals stick;color identity;select .A:14 or .A:15 or .A:16 or .A:17 or .A:19 or .A:20 or .A:21 or .A:22 or .A:41 or .A:63 or .A:64 or .A:65 or .A:66 or .A:94 or .A:95 or .A:96 or .A:97 or .A:122 or .A:147 or .A:148 or .A:149 or .A:155 or .A:158 or .A:161 or .A:165 or .A:191 or .A:192 or .A:193 or .A:194 or .A:196 or .A:198 or .A:199 or .A:218 or .A:222; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLY14
2.621
ILE15
3.409
ILE16
3.215
THR17
4.829
SER19
4.845
SER20
2.480
VAL21
2.788
ALA22
4.318
PHE41
3.328
LEU63
3.104
ASP64
2.874
VAL65
3.010
GLN66
4.159
SER94
3.063
ILE95
3.204
GLY96
3.264
PHE97
4.191
|
|||||
| PDB ID: 2IEB Crystal Structure of Isoniazid-resistant S94A ENOYL-ACP(COA) Reductase Mutant Enzyme from MYCOBACTERIUM TUBERCULOSIS in Complex with NADH-INH | ||||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | Yes | [3] |
| PDB Sequence |
TGLLDGKRIL
11 VSGIITDSSI21 AFHIARVAQE31 QGAQLVLTGF41 DRLRLIQRIT51 DRLPAKAPLL 61 ELDVQNEEHL71 ASLAGRVTEA81 IGAGNKLDGV91 VHAIGFMPQT101 GMGINPFFDA 111 PYADVSKGIH121 ISAYSYASMA131 KALLPIMNPG141 GSIVGMDFDP151 SRAMPAYNWM 161 TVAKSALESV171 NRFVAREAGK181 YGVRSNLVAA191 GPIRTLAMSA201 IVGGALGEEA 211 GAQIQLLEEG221 WDQRAPIGWN231 MKDATPVAKT241 VCALLSDWLP251 ATTGDIIYAD 261 GGAHTQLL
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ZID or .ZID2 or .ZID3 or :3ZID;style chemicals stick;color identity;select .A:14 or .A:15 or .A:16 or .A:17 or .A:19 or .A:20 or .A:21 or .A:22 or .A:41 or .A:63 or .A:64 or .A:65 or .A:66 or .A:94 or .A:95 or .A:96 or .A:97 or .A:122 or .A:147 or .A:148 or .A:149 or .A:155 or .A:158 or .A:161 or .A:165 or .A:191 or .A:192 or .A:193 or .A:194 or .A:196 or .A:198 or .A:199 or .A:218 or .A:222; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLY14
2.605
ILE15
3.545
ILE16
3.239
THR17
4.797
SER19
4.833
SER20
2.607
ILE21
2.815
ALA22
4.407
PHE41
3.328
LEU63
3.156
ASP64
2.948
VAL65
2.967
GLN66
4.214
ALA94
3.148
ILE95
3.224
GLY96
3.238
PHE97
4.188
|
|||||
| PDB ID: 1ZID LONG FATTY ACID CHAIN ENOYL-ACP REDUCTASE (INHA) IN COMPLEX WITH AN ISONICOTINIC-ACYL-NADH INHIBITOR | ||||||
| Method | X-ray diffraction | Resolution | 2.70 Å | Mutation | No | [4] |
| PDB Sequence |
AGLLDGKRIL
11 VSGIITDSSI21 AFHIARVAQE31 QGAQLVLTGF41 DRLRLIQRIT51 DRLPAKAPLL 61 ELDVQNEEHL71 ASLAGRVTEA81 IGAGNKLDGV91 VHSIGFMPQT101 GMGINPFFDA 111 PYADVSKGIH121 ISAYSYASMA131 KALLPIMNPG141 GSIVGMDFDP151 SRAMPAYNWM 161 TVAKSALESV171 NRFVAREAGK181 YGVRSNLVAA191 GPIRTLAMSA201 IVGGALGEEA 211 GAQIQLLEEG221 WDQRAPIGWN231 MKDATPVAKT241 VCALLSDWLP251 ATTGDIIYAD 261 GGAHTQLL
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ZID or .ZID2 or .ZID3 or :3ZID;style chemicals stick;color identity;select .A:14 or .A:15 or .A:16 or .A:17 or .A:20 or .A:21 or .A:22 or .A:40 or .A:41 or .A:63 or .A:64 or .A:65 or .A:66 or .A:94 or .A:95 or .A:96 or .A:97 or .A:122 or .A:147 or .A:148 or .A:149 or .A:155 or .A:158 or .A:161 or .A:165 or .A:191 or .A:192 or .A:193 or .A:194 or .A:195 or .A:196 or .A:198 or .A:199 or .A:218 or .A:222; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLY14
2.464
ILE15
3.500
ILE16
3.595
THR17
4.460
SER20
2.802
ILE21
2.776
ALA22
4.553
GLY40
4.630
PHE41
3.403
LEU63
3.287
ASP64
3.035
VAL65
3.122
GLN66
4.148
SER94
3.482
ILE95
3.238
GLY96
3.177
PHE97
3.889
ILE122
3.341
|
|||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Crystal structure of the enoyl-ACP reductase of Mycobacterium tuberculosis (InhA) in the apo-form and in complex with the active metabolite of isoniazid pre-formed by a biomimetic approach. J Struct Biol. 2015 Jun;190(3):328-37. | ||||
| REF 2 | Transfer of a point mutation in Mycobacterium tuberculosis inhA resolves the target of isoniazid. Nat Med. 2006 Sep;12(9):1027-9. | ||||
| REF 3 | Crystallographic studies on the binding of isonicotinyl-NAD adduct to wild-type and isoniazid resistant 2-trans-enoyl-ACP (CoA) reductase from Mycobacterium tuberculosis. J Struct Biol. 2007 Sep;159(3):369-80. | ||||
| REF 4 | Modification of the NADH of the isoniazid target (InhA) from Mycobacterium tuberculosis. Science. 1998 Jan 2;279(5347):98-102. | ||||
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