6Y2I

Crystal structure of M. tuberculosis KasA in complex with N-(1H-indazol-5-yl)butane-1-sulfonamide

これはPDB形式変換不可エントリーです。

6Y2I の概要

• エントリーDOI: 10.2210/pdb6y2i/pdb
• 分子名称: 3-oxoacyl-[acyl-carrier-protein] synthase 1, 1,2-ETHANEDIOL, ~{N}-(1~{H}-indazol-5-yl)butane-1-sulfonamide, ... (6 entities in total)
• 機能のキーワード: inhibitor, kasa, mycobacterium tuberculosis, 3-oxoacyl-[acyl-carrier-protein] synthase 1, transferase, acyltransferase, lipid synthesis, fatty acid biosynthesis
• 由来する生物種: Mycobacterium tuberculosis H37Rv
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 92362.04

構造登録者

Chung, C. (登録日: 2020-02-16, 公開日: 2020-04-08, 最終更新日: 2024-05-15)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.533 Å)