2WYC

The quorum quenching N-acyl homoserine lactone acylase PvdQ in complex with 3-oxo-lauric acid

2WYC の概要

• エントリーDOI: 10.2210/pdb2wyc/pdb
• 関連するPDBエントリー: 2WYB 2WYD 2WYE
• 分子名称: ACYL-HOMOSERINE LACTONE ACYLASE PVDQ SUBUNIT ALPHA, ACYL-HOMOSERINE LACTONE ACYLASE PVDQ SUBUNIT BETA, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: zymogen, hydrolase, periplasm
• 由来する生物種: PSEUDOMONAS AERUGINOSA; 詳細
• 細胞内の位置: Periplasm (Probable): Q9I194 Q9I194
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 80204.12

構造登録者

Bokhove, M.,Nadal Jimenez, P.,Quax, W.J.,Dijkstra, B.W. (登録日: 2009-11-16, 公開日: 2009-12-29, 最終更新日: 2011-07-13)

主引用文献

Bokhove, M.,Nadal Jimenez, P.,Quax, W.J.,Dijkstra, B.W.
The Quorum-Quenching N-Acyl Homoserine Lactone Acylase Pvdq is an Ntn-Hydrolase with an Unusual Substrate-Binding Pocket
Proc.Natl.Acad.Sci.USA, 107:686-, 2010

PubMed Abstract: In many Gram-negative pathogens, their virulent behavior is regulated by quorum sensing, in which diffusible signals such as N-acyl homoserine lactones (AHLs) act as chemical messaging compounds. Enzymatic degradation of these diffusible signals by, e.g., lactonases or amidohydrolases abolishes AHL regulated virulence, a process known as quorum quenching. Here we report the first crystal structure of an AHL amidohydrolase, the AHL acylase PvdQ from Pseudomonas aeruginosa. PvdQ has a typical alpha/beta heterodimeric Ntn-hydrolase fold, similar to penicillin G acylase and cephalosporin acylase. However, it has a distinct, unusually large, hydrophobic binding pocket, ideally suited to recognize C12 fatty acid-like chains of AHLs. Binding of a C12 fatty acid or a 3-oxo-C12 fatty acid induces subtle conformational changes to accommodate the aliphatic chain. Furthermore, the structure of a covalent ester intermediate identifies Serbeta1 as the nucleophile and Asnbeta269 and Valbeta70 as the oxyanion hole residues in the AHL degradation process. Our structures show the versatility of the Ntn-hydrolase scaffold and can serve as a structural paradigm for Ntn-hydrolases with similar substrate preference. Finally, the quorum-quenching capabilities of PvdQ may be utilized to suppress the quorum-sensing machinery of pathogens.

PubMed: 20080736
DOI: 10.1073/PNAS.0911839107

実験手法

X-RAY DIFFRACTION (1.9 Å)