9MK2

Crystal structure of Neisseria meningitidis ClpP protease complex with noncovalent activator, ACP1-01

これはPDB形式変換不可エントリーです。

9MK2 の概要

• エントリーDOI: 10.2210/pdb9mk2/pdb
• 分子名称: ATP-dependent Clp protease proteolytic subunit, 2-methyl-N-(2-{[2-(trifluoromethyl)phenyl]sulfanyl}ethyl)-2-[5-(trifluoromethyl)pyridine-2-sulfonyl]propanamide (3 entities in total)
• 機能のキーワード: noncovalent, activator, agonist, allosteric, hydrolase
• 由来する生物種: Neisseria meningitidis
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 175387.51

構造登録者

Mabanglo, M.F.,Houry, W.A. (登録日: 2024-12-16, 公開日: 2025-09-03, 最終更新日: 2025-10-15)

主引用文献

Barghash, M.M.,Mabanglo, M.F.,Hoff, S.E.,Brozdnychenko, D.,Wong, K.S.,Binepal, G.,Ip, P.,Shen, J.,Furukawa, T.,Katayama, H.,Trudel, V.,Tan, J.,Yudin, A.K.,Gray-Owen, S.D.,Sakuda, S.,Batey, R.A.,Vahidi, S.,Bonomi, M.,Houry, W.A.
Small molecule dysregulation of ClpP activity via bidirectional allosteric pathways.
Structure, 33:1700-, 2025

PubMed Abstract: The bacterial ClpP protease is essential for the virulence and infectivity of many human pathogens and has emerged as a novel antibacterial drug target. Several classes of small molecules dysregulate or activate ClpP, leading to uncontrolled protein degradation and cell death. Here, we investigate the mechanism of ClpP activation by these compounds using an integrative approach combining structural, biochemical, and computational tools. We identified small molecules that activate ClpP through binding at internal catalytic sites where peptide bond hydrolysis occurs. Combined with knowledge of ClpP activation by small molecules that bind to external hydrophobic sites, this work sheds light on the mechanisms governing ClpP allostery and identifies a common molecular pathway utilized by site-specific effectors to achieve allosteric activation. We propose a consensus, bidirectional ClpP activation mechanism causing protease dysregulation.

PubMed: 40795847
DOI: 10.1016/j.str.2025.07.013

実験手法

X-RAY DIFFRACTION (1.95 Å)