6P9K
Crystal structure of Mycobacterium tuberculosis KasA in complex with O6G
Summary for 6P9K
| Entry DOI | 10.2210/pdb6p9k/pdb |
| Related | 5W2O 5W2P 5W2Q 5W2S |
| Descriptor | 3-oxoacyl-ACP synthase, SODIUM ION, ISOPROPYL ALCOHOL, ... (6 entities in total) |
| Functional Keywords | beta ketoacyl synthase i, lipid synthesis, fatty acid biosynthesis, transferase |
| Biological source | Mycobacterium tuberculosis |
| Total number of polymer chains | 1 |
| Total formula weight | 43848.64 |
| Authors | Capodagli, G.C.,Neiditch, M.B. (deposition date: 2019-06-10, release date: 2020-04-01, Last modification date: 2023-10-11) |
| Primary citation | Inoyama, D.,Awasthi, D.,Capodagli, G.C.,Tsotetsi, K.,Sukheja, P.,Zimmerman, M.,Li, S.G.,Jadhav, R.,Russo, R.,Wang, X.,Grady, C.,Richmann, T.,Shrestha, R.,Li, L.,Ahn, Y.M.,Ho Liang, H.P.,Mina, M.,Park, S.,Perlin, D.S.,Connell, N.,Dartois, V.,Alland, D.,Neiditch, M.B.,Kumar, P.,Freundlich, J.S. A Preclinical Candidate Targeting Mycobacterium tuberculosis KasA. Cell Chem Biol, 27:560-, 2020 Cited by PubMed Abstract: Published Mycobacterium tuberculosis β-ketoacyl-ACP synthase KasA inhibitors lack sufficient potency and/or pharmacokinetic properties. A structure-based approach was used to optimize existing KasA inhibitor DG167. This afforded indazole JSF-3285 with a 30-fold increase in mouse plasma exposure. Biochemical, genetic, and X-ray studies confirmed JSF-3285 targets KasA. JSF-3285 offers substantial activity in an acute mouse model of infection and in the corresponding chronic infection model, with efficacious reductions in colony-forming units at doses as low as 5 mg/kg once daily orally and improvement of the efficacy of front-line drugs isoniazid or rifampicin. JSF-3285 is a promising preclinical candidate for tuberculosis. PubMed: 32197094DOI: 10.1016/j.chembiol.2020.02.007 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.703 Å) |
Structure validation
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