7XHX

Crystal structure of metallo-beta-lactamase IMP-6

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7XHX の概要

• エントリーDOI: 10.2210/pdb7xhx/pdb
• 分子名称: Beta-lactamase, ZINC ION (3 entities in total)
• 機能のキーワード: metallo-beta-lactamase, carbapenemase, zinc protein, hydrolase, antimicrobial protein
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 109023.75

構造登録者

Yamamoto, K.,Tanaka, H.,Kurisu, G.,Nakano, R.,Yano, H.,Sakai, H. (登録日: 2022-04-11, 公開日: 2023-02-15, 最終更新日: 2023-11-29)

主引用文献

Yamamoto, K.,Tanaka, H.,Kurisu, G.,Nakano, R.,Yano, H.,Sakai, H.
Structural insights into the substrate specificity of IMP-6 and IMP-1 metallo-beta-lactamases.
J.Biochem., 173:21-30, 2022

PubMed Abstract: IMP-type metallo-β-lactamases confer resistance to carbapenems and a broad spectrum of β-lactam antibiotics. IMP-6 and IMP-1 differ by only a point mutation: Ser262 in IMP-1 and Gly262 in IMP-6. The kcat/Km values of IMP-1 for imipenem and meropenem are nearly identical; however, for IMP-6, the kcat/Km for meropenem is 7-fold that for imipenem. In clinical practice, this may result in an ineffective therapeutic regimen and, consequently, in treatment failure. Here, we report the crystal structures of IMP-6 and IMP-1 with the same space group and similar cell constants at resolutions of 1.70 and 1.94 Å, respectively. The overall structures of IMP-6 and IMP-1 are similar. However, the loop region (residues 60-66), which participates in substrate binding, is more flexible in IMP-6 than in IMP-1. This difference in flexibility determines the substrate specificity of IMP-type metallo-β-lactamases for imipenem and meropenem. The amino acid at position 262 alters the mobility of His263; this affects the flexibility of the loop via a hydrogen bond with Pro68, which plays the role of a hinge in IMP-type metallo-β-lactamases. The substitution of Pro68 with a glycine elicited an increase in the Km of IMP-6 for imipenem, whereas the affinity for meropenem remained unchanged.

PubMed: 36174533
DOI: 10.1093/jb/mvac080

実験手法

X-RAY DIFFRACTION (1.7 Å)