| Structural highlights
6p9l is a 1 chain structure with sequence from Myctu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , |
| Gene: | kasA, Rv2245, MTCY427.26 (MYCTU) |
| Activity: | [acyl-carrier-protein_synthase_I Beta-ketoacyl-[acyl-carrier-protein] synthase I], with EC number 2.3.1.41 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[FAB1_MYCTU] Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP (By similarity).
Publication Abstract from PubMed
Published Mycobacterium tuberculosis beta-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.
A Preclinical Candidate Targeting Mycobacterium tuberculosis KasA.,Inoyama D, Awasthi D, Capodagli GC, Tsotetsi K, Sukheja P, Zimmerman M, Li SG, Jadhav R, Russo R, Wang X, Grady C, Richmann T, Shrestha R, Li L, Ahn YM, Ho Liang HP, Mina M, Park S, Perlin DS, Connell N, Dartois V, Alland D, Neiditch MB, Kumar P, Freundlich JS Cell Chem Biol. 2020 Mar 19. pii: S2451-9456(20)30071-4. doi:, 10.1016/j.chembiol.2020.02.007. PMID:32197094[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Inoyama D, Awasthi D, Capodagli GC, Tsotetsi K, Sukheja P, Zimmerman M, Li SG, Jadhav R, Russo R, Wang X, Grady C, Richmann T, Shrestha R, Li L, Ahn YM, Ho Liang HP, Mina M, Park S, Perlin DS, Connell N, Dartois V, Alland D, Neiditch MB, Kumar P, Freundlich JS. A Preclinical Candidate Targeting Mycobacterium tuberculosis KasA. Cell Chem Biol. 2020 Mar 19. pii: S2451-9456(20)30071-4. doi:, 10.1016/j.chembiol.2020.02.007. PMID:32197094 doi:http://dx.doi.org/10.1016/j.chembiol.2020.02.007
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