5OIT

InhA (T2A mutant) complexed with 5-((5-Amino-3-methyl-1H-pyrazol-1-yl)methyl)-N-(1-(2-chloro-6-fluorobenzyl)-1H-pyrazol-3-yl)-1,3,4-thiadiazol-2-amine

5OIT の概要

• エントリーDOI: 10.2210/pdb5oit/pdb
• 分子名称: Enoyl-[acyl-carrier-protein] reductase [NADH], 5-[(5-azanyl-3-methyl-pyrazol-1-yl)methyl]-~{N}-[1-[(2-chloranyl-6-fluoranyl-phenyl)methyl]pyrazol-3-yl]-1,3,4-thiadiazol-2-amine, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (4 entities in total)
• 機能のキーワード: inhibitor, complex, fragment based drug discovery, tuberculosis, oxidoreductase
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 118428.23

構造登録者

Convery, M.A. (登録日: 2017-07-19, 公開日: 2018-02-14, 最終更新日: 2024-05-08)

主引用文献

Prati, F.,Zuccotto, F.,Fletcher, D.,Convery, M.A.,Fernandez-Menendez, R.,Bates, R.,Encinas, L.,Zeng, J.,Chung, C.W.,De Dios Anton, P.,Mendoza-Losana, A.,Mackenzie, C.,Green, S.R.,Huggett, M.,Barros, D.,Wyatt, P.G.,Ray, P.C.
Screening of a Novel Fragment Library with Functional Complexity against Mycobacterium tuberculosis InhA.
ChemMedChem, 13:672-677, 2018

PubMed Abstract: Our findings reported herein provide support for the benefits of including functional group complexity (FGC) within fragments when screening against protein targets such as Mycobacterium tuberculosis InhA. We show that InhA fragment actives with FGC maintained their binding pose during elaboration. Furthermore, weak fragment hits with functional group handles also allowed for facile fragment elaboration to afford novel and potent InhA inhibitors with good ligand efficiency metrics for optimization.

PubMed: 29399991
DOI: 10.1002/cmdc.201700774

実験手法

X-RAY DIFFRACTION (2.58 Å)