7DTM

Crystal structure of metallo-beta-lactamase IMP-1 in complex with citrate.

7DTM の概要

• エントリーDOI: 10.2210/pdb7dtm/pdb
• 分子名称: Metallo-beta-lactamase type 2, ZINC ION, CITRATE ANION, ... (4 entities in total)
• 機能のキーワード: metallo-beta-lactamase, zinc(ii) ion, citrate, hydrolase
• 由来する生物種: Serratia marcescens
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 101866.38

構造登録者

Yamaguchi, Y.,Kurosaki, H. (登録日: 2021-01-06, 公開日: 2021-08-04, 最終更新日: 2023-11-29)

主引用文献

Yamaguchi, Y.,Kato, K.,Ichimaru, Y.,Jin, W.,Sakai, M.,Abe, M.,Wachino, J.I.,Arakawa, Y.,Miyagi, Y.,Imai, M.,Fukuishi, N.,Yamagata, Y.,Otsuka, M.,Fujita, M.,Kurosaki, H.
Crystal Structures of Metallo-beta-Lactamase (IMP-1) and Its D120E Mutant in Complexes with Citrate and the Inhibitory Effect of the Benzyl Group in Citrate Monobenzyl Ester.
J.Med.Chem., 64:10019-10026, 2021

PubMed Abstract: The emergence and rapid spread of carbapenem-resistant pathogens producing metallo-β-lactamases such as IMP-1 and NDM-1 have been of great concern in the global clinical setting. The X-ray crystal structures of IMP-1 from and its single mutant, D120E, in complexes with citrate were determined at resolutions of 2.00 and 1.85 Å, respectively. Two crystal structures indicate that a single mutation at position 120 caused a structural change around Zn1, where the geometry changes from a tetrahedron in the native IMP-1 to a square pyramid in D120E. Based on these two complex structures, the authors synthesized citrate monobenzyl ester to evaluate the structural requirement for the inhibitory activity against IMP-1 and compared the inhibitory activities with nonsubstituted citrate. The introduction of a benzyl group into citrate enhanced the inhibitory activity in comparison to citrate (IC > 5 mM).

PubMed: 34242022
DOI: 10.1021/acs.jmedchem.1c00308

実験手法

X-RAY DIFFRACTION (2 Å)