1P44
Targeting tuberculosis and malaria through inhibition of enoyl reductase: compound activity and structural data
Functional Information from GO Data
| Chain | GOid | namespace | contents |
| A | 0004318 | molecular_function | enoyl-[acyl-carrier-protein] reductase (NADH) activity |
| A | 0005504 | molecular_function | fatty acid binding |
| A | 0005886 | cellular_component | plasma membrane |
| A | 0006633 | biological_process | fatty acid biosynthetic process |
| A | 0009274 | cellular_component | peptidoglycan-based cell wall |
| A | 0016491 | molecular_function | oxidoreductase activity |
| A | 0030497 | biological_process | fatty acid elongation |
| A | 0046677 | biological_process | response to antibiotic |
| A | 0050343 | molecular_function | trans-2-enoyl-CoA reductase (NADH) activity |
| A | 0070403 | molecular_function | NAD+ binding |
| A | 0071768 | biological_process | mycolic acid biosynthetic process |
| 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 |
| C | 0004318 | molecular_function | enoyl-[acyl-carrier-protein] reductase (NADH) activity |
| C | 0005504 | molecular_function | fatty acid binding |
| C | 0005886 | cellular_component | plasma membrane |
| C | 0006633 | biological_process | fatty acid biosynthetic process |
| C | 0009274 | cellular_component | peptidoglycan-based cell wall |
| C | 0016491 | molecular_function | oxidoreductase activity |
| C | 0030497 | biological_process | fatty acid elongation |
| C | 0046677 | biological_process | response to antibiotic |
| C | 0050343 | molecular_function | trans-2-enoyl-CoA reductase (NADH) activity |
| C | 0070403 | molecular_function | NAD+ binding |
| C | 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 |
| E | 0004318 | molecular_function | enoyl-[acyl-carrier-protein] reductase (NADH) activity |
| E | 0005504 | molecular_function | fatty acid binding |
| E | 0005886 | cellular_component | plasma membrane |
| E | 0006633 | biological_process | fatty acid biosynthetic process |
| E | 0009274 | cellular_component | peptidoglycan-based cell wall |
| E | 0016491 | molecular_function | oxidoreductase activity |
| E | 0030497 | biological_process | fatty acid elongation |
| E | 0046677 | biological_process | response to antibiotic |
| E | 0050343 | molecular_function | trans-2-enoyl-CoA reductase (NADH) activity |
| E | 0070403 | molecular_function | NAD+ binding |
| E | 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 |
Functional Information from PDB Data
| site_id | AC1 |
| Number of Residues | 24 |
| Details | BINDING SITE FOR RESIDUE NAD A 300 |
| Chain | Residue |
| A | GLY14 |
| A | SER94 |
| A | ILE95 |
| A | GLY96 |
| A | MET147 |
| A | ASP148 |
| A | MET161 |
| A | LYS165 |
| A | ALA191 |
| A | GLY192 |
| A | PRO193 |
| A | ILE15 |
| A | ILE194 |
| A | GEQ350 |
| A | HOH755 |
| A | HOH770 |
| A | HOH815 |
| A | ILE16 |
| A | SER20 |
| A | ILE21 |
| A | PHE41 |
| A | LEU63 |
| A | ASP64 |
| A | VAL65 |
| site_id | AC2 |
| Number of Residues | 25 |
| Details | BINDING SITE FOR RESIDUE NAD B 400 |
| 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 | MET147 |
| B | ASP148 |
| B | PHE149 |
| B | MET161 |
| B | LYS165 |
| B | GLY192 |
| B | PRO193 |
| B | ILE194 |
| B | THR196 |
| B | GEQ450 |
| B | HOH765 |
| B | HOH767 |
| B | HOH860 |
| site_id | AC3 |
| Number of Residues | 20 |
| Details | BINDING SITE FOR RESIDUE NAD C 500 |
| Chain | Residue |
| C | GLY14 |
| C | ILE16 |
| C | SER20 |
| C | ILE21 |
| C | PHE41 |
| C | LEU63 |
| C | ASP64 |
| C | VAL65 |
| C | SER94 |
| C | ILE95 |
| C | GLY96 |
| C | ILE122 |
| C | MET147 |
| C | ASP148 |
| C | PHE149 |
| C | LYS165 |
| C | ILE194 |
| C | THR196 |
| C | GEQ550 |
| C | HOH760 |
| site_id | AC4 |
| Number of Residues | 24 |
| Details | BINDING SITE FOR RESIDUE NAD D 600 |
| Chain | Residue |
| D | GLY14 |
| D | ILE15 |
| 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 | ALA191 |
| D | GLY192 |
| D | PRO193 |
| D | ILE194 |
| D | GEQ650 |
| D | HOH787 |
| D | HOH880 |
| site_id | AC5 |
| Number of Residues | 25 |
| Details | BINDING SITE FOR RESIDUE NAD E 700 |
| Chain | Residue |
| E | ASP64 |
| E | VAL65 |
| E | ILE95 |
| E | GLY96 |
| E | ILE122 |
| E | MET147 |
| E | ASP148 |
| E | PHE149 |
| E | TYR158 |
| E | LYS165 |
| E | ALA191 |
| E | GLY192 |
| E | PRO193 |
| E | ILE194 |
| E | THR196 |
| E | MET199 |
| E | HOH766 |
| E | HOH812 |
| E | HOH861 |
| E | GLY14 |
| E | ILE16 |
| E | SER20 |
| E | ILE21 |
| E | PHE41 |
| E | LEU63 |
| site_id | AC6 |
| Number of Residues | 20 |
| Details | BINDING SITE FOR RESIDUE NAD F 750 |
| Chain | Residue |
| F | GLY14 |
| F | ILE16 |
| F | SER20 |
| F | ILE21 |
| F | PHE41 |
| F | LEU63 |
| F | ASP64 |
| F | VAL65 |
| F | ILE95 |
| F | GLY96 |
| F | ILE122 |
| F | MET147 |
| F | ASP148 |
| F | PHE149 |
| F | LYS165 |
| F | ALA191 |
| F | GLY192 |
| F | PRO193 |
| F | ILE194 |
| F | HOH789 |
| site_id | AC7 |
| Number of Residues | 8 |
| Details | BINDING SITE FOR RESIDUE GEQ A 350 |
| Chain | Residue |
| A | GLY96 |
| A | PHE149 |
| A | ALA157 |
| A | TYR158 |
| A | MET161 |
| A | ILE215 |
| A | LEU218 |
| A | NAD300 |
| site_id | AC8 |
| Number of Residues | 6 |
| Details | BINDING SITE FOR RESIDUE GEQ B 450 |
| Chain | Residue |
| B | GLY96 |
| B | MET103 |
| B | TYR158 |
| B | MET199 |
| B | LEU218 |
| B | NAD400 |
| site_id | AC9 |
| Number of Residues | 7 |
| Details | BINDING SITE FOR RESIDUE GEQ C 550 |
| Chain | Residue |
| C | GLY96 |
| C | MET103 |
| C | TYR158 |
| C | MET161 |
| C | ILE202 |
| C | LEU218 |
| C | NAD500 |
| site_id | BC1 |
| Number of Residues | 6 |
| Details | BINDING SITE FOR RESIDUE GEQ D 650 |
| Chain | Residue |
| D | TYR158 |
| D | MET199 |
| D | ILE202 |
| D | ILE215 |
| D | LEU218 |
| D | NAD600 |
Functional Information from SwissProt/UniProt
| site_id | SWS_FT_FI1 |
| Number of Residues | 30 |
| 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 |
| A | SER20 | |
| B | ILE194 | |
| C | SER20 | |
| C | ASP64 | |
| C | ILE95 | |
| C | LYS165 | |
| C | ILE194 | |
| D | SER20 | |
| D | ASP64 | |
| D | ILE95 | |
| D | LYS165 | |
| A | ASP64 | |
| D | ILE194 | |
| E | SER20 | |
| E | ASP64 | |
| E | ILE95 | |
| E | LYS165 | |
| E | ILE194 | |
| F | SER20 | |
| F | ASP64 | |
| F | ILE95 | |
| F | LYS165 | |
| A | ILE95 | |
| F | ILE194 | |
| A | LYS165 | |
| A | ILE194 | |
| B | SER20 | |
| B | ASP64 | |
| B | ILE95 | |
| B | LYS165 |
| site_id | SWS_FT_FI2 |
| Number of Residues | 6 |
| Details | BINDING: BINDING => ECO:0000269|PubMed:10336454 |
| Chain | Residue | Details |
| A | TYR158 | |
| B | TYR158 | |
| C | TYR158 | |
| D | TYR158 | |
| E | TYR158 | |
| F | TYR158 |
| site_id | SWS_FT_FI3 |
| Number of Residues | 6 |
| Details | SITE: May act as an intermediate that passes the hydride ion from NADH to the substrate => ECO:0000305|PubMed:10336454 |
| Chain | Residue | Details |
| A | PHE149 | |
| B | PHE149 | |
| C | PHE149 | |
| D | PHE149 | |
| E | PHE149 | |
| F | PHE149 |
| site_id | SWS_FT_FI4 |
| Number of Residues | 6 |
| Details | SITE: Transition state stabilizer => ECO:0000305|PubMed:10521269 |
| Chain | Residue | Details |
| A | TYR158 | |
| B | TYR158 | |
| C | TYR158 | |
| D | TYR158 | |
| E | TYR158 | |
| F | TYR158 |
| site_id | SWS_FT_FI5 |
| Number of Residues | 6 |
| Details | MOD_RES: Phosphothreonine => ECO:0000269|PubMed:20864541, ECO:0000269|PubMed:21143326 |
| Chain | Residue | Details |
| A | THR266 | |
| B | THR266 | |
| C | THR266 | |
| D | THR266 | |
| E | THR266 | |
| F | THR266 |
Catalytic Information from CSA
| site_id | CSA1 |
| Number of Residues | 2 |
| Details | Annotated By Reference To The Literature 1qsg |
| Chain | Residue | Details |
| A | TYR158 | |
| A | LYS165 |
| site_id | CSA10 |
| Number of Residues | 2 |
| Details | Annotated By Reference To The Literature 1qsg |
| Chain | Residue | Details |
| D | MET161 | |
| D | LYS165 |
| site_id | CSA11 |
| Number of Residues | 2 |
| Details | Annotated By Reference To The Literature 1qsg |
| Chain | Residue | Details |
| E | MET161 | |
| E | LYS165 |
| site_id | CSA12 |
| Number of Residues | 2 |
| Details | Annotated By Reference To The Literature 1qsg |
| Chain | Residue | Details |
| F | MET161 | |
| F | LYS165 |
| site_id | CSA2 |
| Number of Residues | 2 |
| Details | Annotated By Reference To The Literature 1qsg |
| Chain | Residue | Details |
| B | TYR158 | |
| B | LYS165 |
| site_id | CSA3 |
| Number of Residues | 2 |
| Details | Annotated By Reference To The Literature 1qsg |
| Chain | Residue | Details |
| C | TYR158 | |
| C | LYS165 |
| site_id | CSA4 |
| Number of Residues | 2 |
| Details | Annotated By Reference To The Literature 1qsg |
| Chain | Residue | Details |
| D | TYR158 | |
| D | LYS165 |
| site_id | CSA5 |
| Number of Residues | 2 |
| Details | Annotated By Reference To The Literature 1qsg |
| Chain | Residue | Details |
| E | TYR158 | |
| E | LYS165 |
| site_id | CSA6 |
| Number of Residues | 2 |
| Details | Annotated By Reference To The Literature 1qsg |
| Chain | Residue | Details |
| F | TYR158 | |
| F | LYS165 |
| site_id | CSA7 |
| Number of Residues | 2 |
| Details | Annotated By Reference To The Literature 1qsg |
| Chain | Residue | Details |
| A | MET161 | |
| A | LYS165 |
| site_id | CSA8 |
| Number of Residues | 2 |
| Details | Annotated By Reference To The Literature 1qsg |
| Chain | Residue | Details |
| B | MET161 | |
| B | LYS165 |
| site_id | CSA9 |
| Number of Residues | 2 |
| Details | Annotated By Reference To The Literature 1qsg |
| Chain | Residue | Details |
| C | MET161 | |
| C | LYS165 |
