3WXC

Crystal Structure of IMP-1 metallo-beta-lactamase complexed with a 3-aminophtalic acid inhibitor

3WXC の概要

• エントリーDOI: 10.2210/pdb3wxc/pdb
• 分子名称: Beta-lactamase, ZINC ION, 3-(4-hydroxypiperidin-1-yl)benzene-1,2-dicarboxylic acid, ... (4 entities in total)
• 機能のキーワード: lactamase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Pseudomonas aeruginosa
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 49862.17

構造登録者

Saito, J.,Watanabe, T.,Yamada, M. (登録日: 2014-07-29, 公開日: 2014-10-15, 最終更新日: 2024-04-03)

主引用文献

Hiraiwa, Y.,Saito, J.,Watanabe, T.,Yamada, M.,Morinaka, A.,Fukushima, T.,Kudo, T.
X-ray crystallographic analysis of IMP-1 metallo-beta-lactamase complexed with a 3-aminophthalic acid derivative, structure-based drug design, and synthesis of 3,6-disubstituted phthalic acid derivative inhibitors
Bioorg.Med.Chem.Lett., 24:4891-4894, 2014

PubMed Abstract: 3-(4-Hydroxypiperidine-1-yl) phthalic acid 1 shows potent inhibitory activity against metallo-β-lactamase, which is known to inactivate β-lactam antibiotics such as carbapenems. Here, the structure of co-crystals of the metallo-β-lactamase IMP-1 and 1 was first analyzed by X-ray crystallography, and then used for structure-based drug design. Four novel compounds bearing substituents at the 6-position were synthesized to produce 3,6-disubstituted phthalic acid derivatives, and their IMP-1 inhibitory activity and synergistic effect with the carbapenem biapenem (BIPM) were evaluated. 3,6-Disubstituted phthalic acid derivatives showed potent IMP-1 inhibitory activity. In particular, compound 13 showed 10-fold higher IMP-1 inhibitory activity as compared with the parent derivative 1.

PubMed: 25246278
DOI: 10.1016/j.bmcl.2014.08.039

実験手法

X-RAY DIFFRACTION (2.1 Å)