7KYF

Botulism Neurooxin Light Chain A app form

7KYF の概要

• エントリーDOI: 10.2210/pdb7kyf/pdb
• 分子名称: Bont/A1, ZINC ION, N-[(3,5-dichlorophenyl)sulfonyl]-L-isoleucyl-N-hydroxy-L-norvalinamide, ... (4 entities in total)
• 機能のキーワード: bont, botulinum neurotoxin nva-ila dipetpide bound, toxin
• 由来する生物種: Clostridium botulinum
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 48296.82

構造登録者

Ortega, M.E.,Salzameda, N.T. (登録日: 2020-12-07, 公開日: 2021-04-14, 最終更新日: 2023-10-18)

主引用文献

Amezcua, M.,Cruz, R.S.,Ku, A.,Moran, W.,Ortega, M.E.,Salzameda, N.T.
Discovery of Dipeptides as Potent Botulinum Neurotoxin A Light-Chain Inhibitors.
Acs Med.Chem.Lett., 12:295-301, 2021

PubMed Abstract: The botulinum neurotoxin, the caustic agent that causes botulism, is the most lethal toxin known to man. The neurotoxin composed of a heavy chain (HC) and a light chain (LC) enters neurons and cleaves SNARE proteins, leading to flaccid paralysis, which, in severe occurrences, can result in death. A therapeutic target for botulinum neurotoxin (BoNT) intoxication is the LC, a zinc metalloprotease that directly cleaves SNARE proteins. Herein we report dipeptides containing an aromatic connected to the N-terminus via a sulfonamide and a hydroxamic acid at the C-terminus as BoNT/A LC inhibitors. On the basis of a structure-activity relationship study, was discovered to inhibit the BoNT/A LC with an IC of 21 nM. X-ray crystallography analysis of and revealed that the dipeptides inhibit through a competitive mechanism and identified several key intermolecular interactions.

PubMed: 33603978
DOI: 10.1021/acsmedchemlett.0c00674

実験手法

X-RAY DIFFRACTION (2.33 Å)