6SQL

Crystal structure of M. tuberculosis InhA in complex with NAD+ and N-(3-(aminomethyl)phenyl)-5-chloro-3-methylbenzo[b]thiophene-2-sulfonamide

6SQL の概要

• エントリーDOI: 10.2210/pdb6sql/pdb
• 分子名称: Enoyl-[acyl-carrier-protein] reductase [NADH], NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ~{N}-[3-(aminomethyl)phenyl]-5-chloranyl-3-methyl-1-benzothiophene-2-sulfonamide, ... (4 entities in total)
• 機能のキーワード: inha, nadh-dependent enoyl-[acyl-carrier-protein] reductase, oxidoreductase
• 由来する生物種: Mycobacterium tuberculosis H37Rv
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29672.17

構造登録者

Mendes, V.,Sabbah, M.,Coyne, A.G.,Abell, C.,Blundell, T.L. (登録日: 2019-09-04, 公開日: 2020-04-22, 最終更新日: 2024-01-24)

主引用文献

Sabbah, M.,Mendes, V.,Vistal, R.G.,Dias, D.M.G.,Zahorszka, M.,Mikusova, K.,Kordulakova, J.,Coyne, A.G.,Blundell, T.L.,Abell, C.
Fragment-Based Design ofMycobacterium tuberculosisInhA Inhibitors.
J.Med.Chem., 63:4749-4761, 2020

PubMed Abstract: Tuberculosis (TB) remains a leading cause of mortality among infectious diseases worldwide. InhA has been the focus of numerous drug discovery efforts as this is the target of the first line pro-drug isoniazid. However, with resistance to this drug becoming more common, the aim has been to find new clinical candidates that directly inhibit this enzyme and that do not require activation by the catalase peroxidase KatG, thus circumventing the majority of the resistance mechanisms. In this work, the screening and validation of a fragment library are described, and the development of the fragment hits using a fragment growing strategy was employed, which led to the development of InhA inhibitors with affinities of up to 250 nM.

PubMed: 32240584
DOI: 10.1021/acs.jmedchem.0c00007

実験手法

X-RAY DIFFRACTION (2.35 Å)