3NY6

Catalytic fragment of cholix toxin from vibrio cholerae in complex with inhibitor V30

3NY6 の概要

• エントリーDOI: 10.2210/pdb3ny6/pdb
• 関連するPDBエントリー: 2Q6M 3ESS 3KI0 3KI1 3KI2 3KI3 3KI4 3KI5 3KI6 3KI7
• 分子名称: Cholix toxin, GLYCEROL, 2-[(5,6-dimethyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-2-yl)sulfanyl]-N-(2-hydroxyethyl)acetamide, ... (5 entities in total)
• 機能のキーワード: alpha-beta complex, adp-ribosyl transferase, nad+ binding, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Vibrio cholerae
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23927.40

構造登録者

Merrill, A.R.,Jorgensen, R. (登録日: 2010-07-14, 公開日: 2010-12-29, 最終更新日: 2023-09-06)

主引用文献

Turgeon, Z.,Jorgensen, R.,Visschedyk, D.,Edwards, P.R.,Legree, S.,McGregor, C.,Fieldhouse, R.J.,Mangroo, D.,Schapira, M.,Merrill, A.R.
Newly discovered and characterized antivirulence compounds inhibit bacterial mono-ADP-ribosyltransferase toxins.
Antimicrob.Agents Chemother., 55:983-991, 2011

PubMed Abstract: The mono-ADP-ribosyltransferase toxins are bacterial virulence factors that contribute to many disease states in plants, animals, and humans. These toxins function as enzymes that target various host proteins and covalently attach an ADP-ribose moiety that alters target protein function. We tested compounds from a virtual screen of commercially available compounds combined with a directed poly(ADP-ribose) polymerase (PARP) inhibitor library and found several compounds that bind tightly and inhibit toxins from Pseudomonas aeruginosa and Vibrio cholerae. The most efficacious compounds completely protected human lung epithelial cells against the cytotoxicity of these bacterial virulence factors. Moreover, we determined high-resolution crystal structures of the best inhibitors in complex with cholix toxin to reveal important criteria for inhibitor binding and mechanism of action. These results provide new insight into development of antivirulence compounds for treating many bacterial diseases.

PubMed: 21135177
DOI: 10.1128/AAC.01164-10

実験手法

X-RAY DIFFRACTION (1.68 Å)