3GCD

Structure of the V. cholerae RTX cysteine protease domain in complex with an aza-Leucine peptide inhibitor

3GCD の概要

• エントリーDOI: 10.2210/pdb3gcd/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000439
• 分子名称: RTX toxin RtxA, ethyl (5S,8S,14S)-14-hydroxy-5,8,11-tris(2-methylpropyl)-3,6,9,12-tetraoxo-1-phenyl-2-oxa-4,7,10,11-tetraazapentadecan-15-oate, INOSITOL HEXAKISPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: v. cholerae, repeats-in-toxin, martx, cysteine protease, inositol hexakisphosphate, aza-peptide, aza-leu, toxin-inhibitor complex, toxin/inhibitor
• 由来する生物種: Vibrio cholerae
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 95942.68

構造登録者

Lupardus, P.J.,Garcia, K.C.,Shen, A.,Bogyo, M. (登録日: 2009-02-21, 公開日: 2009-05-26, 最終更新日: 2024-11-20)

主引用文献

Shen, A.,Lupardus, P.J.,Albrow, V.E.,Guzzetta, A.,Powers, J.C.,Garcia, K.C.,Bogyo, M.
Mechanistic and structural insights into the proteolytic activation of Vibrio cholerae MARTX toxin.
Nat.Chem.Biol., 5:469-478, 2009

PubMed Abstract: MARTX toxins modulate the virulence of a number of Gram-negative Vibrio species. This family of toxins is defined by the presence of a cysteine protease domain (CPD), which proteolytically activates the Vibrio cholerae MARTX toxin. Although recent structural studies of the CPD have uncovered a new allosteric activation mechanism, the mechanism of CPD substrate recognition or toxin processing is unknown. Here we show that interdomain cleavage of MARTXVc enhances effector domain function. We also identify the first small-molecule inhibitors of this protease domain and present the 2.35-A structure of the CPD bound to one of these inhibitors. This structure, coupled with biochemical and mutational studies of the toxin, reveals the molecular basis of CPD substrate specificity and underscores the evolutionary relationship between the CPD and the clan CD caspase proteases. These studies are likely to prove valuable for devising new antitoxin strategies for a number of bacterial pathogens.

PubMed: 19465933
DOI: 10.1038/nchembio.178

実験手法

X-RAY DIFFRACTION (2.35 Å)