2YZ3

Crystallographic Investigation of Inhibition Mode of the VIM-2 Metallo-beta-lactamase from Pseudomonas aeruginosa with Mercaptocarboxylate Inhibitor

2YZ3 の概要

• エントリーDOI: 10.2210/pdb2yz3/pdb
• 分子名称: Metallo-beta-lactamase, ZINC ION, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: metallo-beta-lactamase, enzyme-inhibitor complex, hydrolase
• 由来する生物種: Pseudomonas putida
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 57800.20

構造登録者

Yamaguchi, Y.,Yamagata, Y.,Arakawa, Y.,Kurosaki, H. (登録日: 2007-05-02, 公開日: 2008-03-11, 最終更新日: 2024-03-13)

主引用文献

Yamaguchi, Y.,Jin, W.,Matsunaga, K.,Ikemizu, S.,Yamagata, Y.,Wachino, J.,Shibata, N.,Arakawa, Y.,Kurosaki, H.
Crystallographic investigation of the inhibition mode of a VIM-2 metallo-beta-lactamase from Pseudomonas aeruginosa by a mercaptocarboxylate inhibitor.
J.Med.Chem., 50:6647-6653, 2007

PubMed Abstract: The VIM-2 metallo-beta-lactamase enzyme from Pseudomonas aeruginosa catalyzes the hydrolysis of most beta-lactam antibiotics including carbapenems, and there are currently no potent inhibitors of such enzymes. We found rac-2-omega-phenylpropyl-3-mercaptopropionic acid, phenylC3SH, to be a potent inhibitor of VIM-2. The structure of the VIM-2-phenylC3SH complex was determined by X-ray crystallography to 2.3 A. The structure revealed that the thiol group of phenylC3SH bridged to the two zinc(II) ions and the phenyl group interacted with Tyr67(47) on loop1 near the active site, by pi-pi stacking interactions. The methylene group interacted with Phe61(42) located at the bottom of loop1 through CH-pi interactions. Dynamic movements were observed in Arg228(185) and Asn233(190) on loop2, compared with the native structure (PDB code: 1KO3 ). These results suggest that the above-mentioned four residues play important roles in the binding and recognition of inhibitors or substrates and in stabilizing a loop in the VIM-2 enzyme.

PubMed: 18052313
DOI: 10.1021/jm701031n

実験手法

X-RAY DIFFRACTION (2.3 Å)