6Y2J

Crystal structure of M. tuberculosis KasA in complex with 4,4,4-trifluoro-N-(isoquinolin-6-yl)butane-1-sulfonamide

This is a non-PDB format compatible entry.

Summary for 6Y2J

• Entry DOI: 10.2210/pdb6y2j/pdb
• Descriptor: 3-oxoacyl-[acyl-carrier-protein] synthase 1, TETRAETHYLENE GLYCOL, SODIUM ION, ... (5 entities in total)
• Functional Keywords: inhibitor, kasa, mycobacterium tuberculosis, 3-oxoacyl-[acyl-carrier-protein] synthase 1, transferase, acyltransferase, lipid synthesis, fatty acid biosynthesis
• Biological source: Mycobacterium tuberculosis H37Rv
• Total number of polymer chains: 8
• Total formula weight: 367485.41

Authors

Chung, C. (deposition date: 2020-02-16, release date: 2020-04-08, Last modification date: 2024-05-15)

Primary citation

Cunningham, F.,Esquivias, J.,Fernandez-Menendez, R.,Perez, A.,Guardia, A.,Escribano, J.,Rivero, C.,Vimal, M.,Cacho, M.,de Dios-Anton, P.,Martinez-Martinez, M.S.,Jimenez, E.,Huertas Valentin, L.,Rebollo-Lopez, M.J.,Lopez-Roman, E.M.,Sousa-Morcuende, V.,Rullas, J.,Neu, M.,Chung, C.W.,Bates, R.H.
Exploring the SAR of the beta-Ketoacyl-ACP Synthase Inhibitor GSK3011724A and Optimization around a Genotoxic Metabolite.
Acs Infect Dis., 6:1098-1109, 2020

PubMed Abstract: In the course of optimizing a novel indazole sulfonamide series that inhibits β-ketoacyl-ACP synthase (KasA) of , a mutagenic aniline metabolite was identified. Further lead optimization efforts were therefore dedicated to eliminating this critical liability by removing the embedded aniline moiety or modifying its steric or electronic environment. While the narrow SAR space against the target ultimately rendered this goal unsuccessful, key structural knowledge around the binding site of this underexplored target for TB was generated to inform future discovery efforts.

PubMed: 32196311
DOI: 10.1021/acsinfecdis.9b00493

Experimental method

X-RAY DIFFRACTION (2.886 Å)