5JFO
Structure of the M.tuberculosis enoyl-reductase InhA in complex with GSK625
Summary for 5JFO
| Entry DOI | 10.2210/pdb5jfo/pdb |
| Descriptor | Enoyl-[acyl-carrier-protein] reductase [NADH], NICOTINAMIDE-ADENINE-DINUCLEOTIDE, N-{1-[(2-chloro-6-fluorophenyl)methyl]-1H-pyrazol-3-yl}-5-[(1S)-1-(3-methyl-1H-pyrazol-1-yl)ethyl]-1,3,4-thiadiazol-2-amine, ... (4 entities in total) |
| Functional Keywords | antitubercular, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor |
| Biological source | Mycobacterium tuberculosis |
| Total number of polymer chains | 4 |
| Total formula weight | 118544.39 |
| Authors | Gulten, G.,Sacchettini, J.C. (deposition date: 2016-04-19, release date: 2016-08-10, Last modification date: 2023-09-27) |
| Primary citation | Martinez-Hoyos, M.,Perez-Herran, E.,Gulten, G.,Encinas, L.,Alvarez-Gomez, D.,Alvarez, E.,Ferrer-Bazaga, S.,Garcia-Perez, A.,Ortega, F.,Angulo-Barturen, I.,Rullas-Trincado, J.,Blanco Ruano, D.,Torres, P.,Castaneda, P.,Huss, S.,Fernandez Menendez, R.,Gonzalez Del Valle, S.,Ballell, L.,Barros, D.,Modha, S.,Dhar, N.,Signorino-Gelo, F.,McKinney, J.D.,Garcia-Bustos, J.F.,Lavandera, J.L.,Sacchettini, J.C.,Jimenez, M.S.,Martin-Casabona, N.,Castro-Pichel, J.,Mendoza-Losana, A. Antitubercular drugs for an old target: GSK693 as a promising InhA direct inhibitor. Ebiomedicine, 8:291-301, 2016 Cited by PubMed Abstract: Despite being one of the first antitubercular agents identified, isoniazid (INH) is still the most prescribed drug for prophylaxis and tuberculosis (TB) treatment and, together with rifampicin, the pillars of current chemotherapy. A high percentage of isoniazid resistance is linked to mutations in the pro-drug activating enzyme KatG, so the discovery of direct inhibitors (DI) of the enoyl-ACP reductase (InhA) has been pursued by many groups leading to the identification of different enzyme inhibitors, active against Mycobacterium tuberculosis (Mtb), but with poor physicochemical properties to be considered as preclinical candidates. Here, we present a series of InhA DI active against multidrug (MDR) and extensively (XDR) drug-resistant clinical isolates as well as in TB murine models when orally dosed that can be a promising foundation for a future treatment. PubMed: 27428438DOI: 10.1016/j.ebiom.2016.05.006 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.907 Å) |
Structure validation
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