4COD
Encoded library technology as a source of hits for the discovery and lead optimization of a potent and selective class of bactericidal direct inhibitors of Mycobacterium tuberculosis InhA
Functional Information from GO Data
| Chain | GOid | namespace | contents |
| B | 0004318 | molecular_function | enoyl-[acyl-carrier-protein] reductase (NADH) activity |
| B | 0005504 | molecular_function | fatty acid binding |
| B | 0005886 | cellular_component | plasma membrane |
| B | 0006633 | biological_process | fatty acid biosynthetic process |
| B | 0009274 | cellular_component | peptidoglycan-based cell wall |
| B | 0016491 | molecular_function | oxidoreductase activity |
| B | 0030497 | biological_process | fatty acid elongation |
| B | 0046677 | biological_process | response to antibiotic |
| B | 0050343 | molecular_function | trans-2-enoyl-CoA reductase (NADH) activity |
| B | 0070403 | molecular_function | NAD+ binding |
| B | 0071768 | biological_process | mycolic acid biosynthetic process |
| D | 0004318 | molecular_function | enoyl-[acyl-carrier-protein] reductase (NADH) activity |
| D | 0005504 | molecular_function | fatty acid binding |
| D | 0005886 | cellular_component | plasma membrane |
| D | 0006633 | biological_process | fatty acid biosynthetic process |
| D | 0009274 | cellular_component | peptidoglycan-based cell wall |
| D | 0016491 | molecular_function | oxidoreductase activity |
| D | 0030497 | biological_process | fatty acid elongation |
| D | 0046677 | biological_process | response to antibiotic |
| D | 0050343 | molecular_function | trans-2-enoyl-CoA reductase (NADH) activity |
| D | 0070403 | molecular_function | NAD+ binding |
| D | 0071768 | biological_process | mycolic acid biosynthetic process |
| F | 0004318 | molecular_function | enoyl-[acyl-carrier-protein] reductase (NADH) activity |
| F | 0005504 | molecular_function | fatty acid binding |
| F | 0005886 | cellular_component | plasma membrane |
| F | 0006633 | biological_process | fatty acid biosynthetic process |
| F | 0009274 | cellular_component | peptidoglycan-based cell wall |
| F | 0016491 | molecular_function | oxidoreductase activity |
| F | 0030497 | biological_process | fatty acid elongation |
| F | 0046677 | biological_process | response to antibiotic |
| F | 0050343 | molecular_function | trans-2-enoyl-CoA reductase (NADH) activity |
| F | 0070403 | molecular_function | NAD+ binding |
| F | 0071768 | biological_process | mycolic acid biosynthetic process |
| H | 0004318 | molecular_function | enoyl-[acyl-carrier-protein] reductase (NADH) activity |
| H | 0005504 | molecular_function | fatty acid binding |
| H | 0005886 | cellular_component | plasma membrane |
| H | 0006633 | biological_process | fatty acid biosynthetic process |
| H | 0009274 | cellular_component | peptidoglycan-based cell wall |
| H | 0016491 | molecular_function | oxidoreductase activity |
| H | 0030497 | biological_process | fatty acid elongation |
| H | 0046677 | biological_process | response to antibiotic |
| H | 0050343 | molecular_function | trans-2-enoyl-CoA reductase (NADH) activity |
| H | 0070403 | molecular_function | NAD+ binding |
| H | 0071768 | biological_process | mycolic acid biosynthetic process |
Functional Information from PDB Data
| site_id | AC1 |
| Number of Residues | 16 |
| Details | BINDING SITE FOR RESIDUE KV1 B 1270 |
| Chain | Residue |
| B | GLY96 |
| B | LEU197 |
| B | ALA198 |
| B | MET199 |
| B | SER200 |
| B | ALA201 |
| B | ILE202 |
| B | NAD1271 |
| B | PHE97 |
| B | MET98 |
| B | MET103 |
| B | GLY104 |
| B | PHE149 |
| B | ALA157 |
| B | TYR158 |
| B | MET161 |
| site_id | AC2 |
| Number of Residues | 31 |
| Details | BINDING SITE FOR RESIDUE NAD B 1271 |
| Chain | Residue |
| B | GLY14 |
| B | ILE15 |
| B | ILE16 |
| B | SER20 |
| B | ILE21 |
| B | PHE41 |
| B | LEU63 |
| B | ASP64 |
| B | VAL65 |
| B | SER94 |
| B | ILE95 |
| B | GLY96 |
| B | ILE122 |
| B | MET147 |
| B | ASP148 |
| B | PHE149 |
| B | LYS165 |
| B | ALA191 |
| B | GLY192 |
| B | PRO193 |
| B | ILE194 |
| B | THR196 |
| B | ALA198 |
| B | KV11270 |
| B | HOH2006 |
| B | HOH2007 |
| B | HOH2008 |
| B | HOH2061 |
| B | HOH2095 |
| B | HOH2142 |
| B | HOH2143 |
| site_id | AC3 |
| Number of Residues | 14 |
| Details | BINDING SITE FOR RESIDUE KV1 D 1270 |
| Chain | Residue |
| D | GLY96 |
| D | PHE97 |
| D | MET98 |
| D | MET103 |
| D | GLY104 |
| D | TYR158 |
| D | MET161 |
| D | LEU197 |
| D | ALA198 |
| D | MET199 |
| D | SER200 |
| D | ALA201 |
| D | ILE202 |
| D | NAD1271 |
| site_id | AC4 |
| Number of Residues | 25 |
| Details | BINDING SITE FOR RESIDUE NAD D 1271 |
| Chain | Residue |
| D | GLY14 |
| D | ILE16 |
| D | SER20 |
| D | ILE21 |
| D | PHE41 |
| D | LEU63 |
| D | ASP64 |
| D | VAL65 |
| D | SER94 |
| D | ILE95 |
| D | GLY96 |
| D | ILE122 |
| D | MET147 |
| D | ASP148 |
| D | PHE149 |
| D | LYS165 |
| D | GLY192 |
| D | PRO193 |
| D | ILE194 |
| D | THR196 |
| D | ALA198 |
| D | KV11270 |
| D | HOH2004 |
| D | HOH2055 |
| D | HOH2115 |
| site_id | AC5 |
| Number of Residues | 28 |
| Details | BINDING SITE FOR RESIDUE NAD F 1270 |
| Chain | Residue |
| F | ASP148 |
| F | PHE149 |
| F | LYS165 |
| F | PRO193 |
| F | ILE194 |
| F | THR196 |
| F | ALA198 |
| F | MET199 |
| F | KV11271 |
| F | HOH2002 |
| F | HOH2003 |
| F | HOH2005 |
| F | HOH2036 |
| F | HOH2037 |
| F | HOH2075 |
| F | GLY14 |
| F | ILE16 |
| F | SER20 |
| F | ILE21 |
| F | PHE41 |
| F | LEU63 |
| F | ASP64 |
| F | VAL65 |
| F | SER94 |
| F | ILE95 |
| F | GLY96 |
| F | ILE122 |
| F | MET147 |
| site_id | AC6 |
| Number of Residues | 17 |
| Details | BINDING SITE FOR RESIDUE KV1 F 1271 |
| Chain | Residue |
| F | GLY96 |
| F | PHE97 |
| F | MET98 |
| F | MET103 |
| F | GLY104 |
| F | PHE149 |
| F | ALA157 |
| F | TYR158 |
| F | MET161 |
| F | LEU197 |
| F | ALA198 |
| F | MET199 |
| F | SER200 |
| F | ALA201 |
| F | ILE202 |
| F | LEU207 |
| F | NAD1270 |
| site_id | AC7 |
| Number of Residues | 16 |
| Details | BINDING SITE FOR RESIDUE KV1 H 1270 |
| Chain | Residue |
| H | GLY96 |
| H | PHE97 |
| H | MET98 |
| H | MET103 |
| H | GLY104 |
| H | ALA157 |
| H | TYR158 |
| H | MET161 |
| H | LEU197 |
| H | ALA198 |
| H | MET199 |
| H | SER200 |
| H | ALA201 |
| H | ILE202 |
| H | LEU207 |
| H | NAD1271 |
| site_id | AC8 |
| Number of Residues | 28 |
| Details | BINDING SITE FOR RESIDUE NAD H 1271 |
| Chain | Residue |
| H | GLY14 |
| H | ILE15 |
| H | ILE16 |
| H | SER20 |
| H | ILE21 |
| H | PHE41 |
| H | LEU63 |
| H | ASP64 |
| H | VAL65 |
| H | SER94 |
| H | ILE95 |
| H | GLY96 |
| H | ILE122 |
| H | MET147 |
| H | ASP148 |
| H | PHE149 |
| H | LYS165 |
| H | GLY192 |
| H | PRO193 |
| H | ILE194 |
| H | THR196 |
| H | ALA198 |
| H | MET199 |
| H | KV11270 |
| H | HOH2004 |
| H | HOH2005 |
| H | HOH2020 |
| H | HOH2047 |
Functional Information from SwissProt/UniProt
| site_id | SWS_FT_FI1 |
| Number of Residues | 20 |
| Details | BINDING: BINDING => ECO:0000269|PubMed:10336454, ECO:0000269|PubMed:16647717, ECO:0000269|PubMed:7886450, ECO:0007744|PDB:1BVR, ECO:0007744|PDB:1ENY, ECO:0007744|PDB:2AQ8 |
| Chain | Residue | Details |
| B | SER20 | |
| D | ILE194 | |
| F | SER20 | |
| F | ASP64 | |
| F | ILE95 | |
| F | LYS165 | |
| F | ILE194 | |
| H | SER20 | |
| H | ASP64 | |
| H | ILE95 | |
| H | LYS165 | |
| B | ASP64 | |
| H | ILE194 | |
| B | ILE95 | |
| B | LYS165 | |
| B | ILE194 | |
| D | SER20 | |
| D | ASP64 | |
| D | ILE95 | |
| D | LYS165 |
| site_id | SWS_FT_FI2 |
| Number of Residues | 4 |
| Details | BINDING: BINDING => ECO:0000269|PubMed:10336454 |
| Chain | Residue | Details |
| B | TYR158 | |
| D | TYR158 | |
| F | TYR158 | |
| H | TYR158 |
| site_id | SWS_FT_FI3 |
| Number of Residues | 4 |
| Details | SITE: May act as an intermediate that passes the hydride ion from NADH to the substrate => ECO:0000305|PubMed:10336454 |
| Chain | Residue | Details |
| B | PHE149 | |
| D | PHE149 | |
| F | PHE149 | |
| H | PHE149 |
| site_id | SWS_FT_FI4 |
| Number of Residues | 4 |
| Details | SITE: Transition state stabilizer => ECO:0000305|PubMed:10521269 |
| Chain | Residue | Details |
| B | TYR158 | |
| D | TYR158 | |
| F | TYR158 | |
| H | TYR158 |
| site_id | SWS_FT_FI5 |
| Number of Residues | 4 |
| Details | MOD_RES: Phosphothreonine => ECO:0000269|PubMed:20864541, ECO:0000269|PubMed:21143326 |
| Chain | Residue | Details |
| B | THR266 | |
| D | THR266 | |
| F | THR266 | |
| H | THR266 |
