5IQK

Rm3 metallo-beta-lactamase

5IQK の概要

• エントリーDOI: 10.2210/pdb5iqk/pdb
• 分子名称: beta-lactamase Rm3, ZINC ION (3 entities in total)
• 機能のキーワード: lactamase, metallo, metagenomic, antibiotic resistance, hydrolase
• 由来する生物種: uncultured bacterium
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 58412.88

構造登録者

Salimraj, R.,Spencer, J. (登録日: 2016-03-10, 公開日: 2016-03-23, 最終更新日: 2024-10-16)

主引用文献

Salimraj, R.,Zhang, L.,Hinchliffe, P.,Wellington, E.M.,Brem, J.,Schofield, C.J.,Gaze, W.H.,Spencer, J.
Structural and Biochemical Characterization of Rm3, a Subclass B3 Metallo-beta-Lactamase Identified from a Functional Metagenomic Study.
Antimicrob.Agents Chemother., 60:5828-5840, 2016

PubMed Abstract: β-Lactamase production increasingly threatens the effectiveness of β-lactams, which remain a mainstay of antimicrobial chemotherapy. New activities emerge through both mutation of previously known β-lactamases and mobilization from environmental reservoirs. The spread of metallo-β-lactamases (MBLs) represents a particular challenge because of their typically broad-spectrum activities encompassing carbapenems, in addition to other β-lactam classes. Increasingly, genomic and metagenomic studies have revealed the distribution of putative MBLs in the environment, but in most cases their activity against clinically relevant β-lactams and, hence, the extent to which they can be considered a resistance reservoir remain uncharacterized. Here we characterize the product of one such gene, blaRm3, identified through functional metagenomic sampling of an environment with high levels of biocide exposure. blaRm3 encodes a subclass B3 MBL that, when expressed in a recombinant Escherichia coli strain, is exported to the bacterial periplasm and hydrolyzes clinically used penicillins, cephalosporins, and carbapenems with an efficiency limited by high Km values. An Rm3 crystal structure reveals the MBL superfamily αβ/βα fold, which more closely resembles that in mobilized B3 MBLs (AIM-1 and SMB-1) than other chromosomal enzymes (L1 or FEZ-1). A binuclear zinc site sits in a deep channel that is in part defined by a relatively extended N terminus. Structural comparisons suggest that the steric constraints imposed by the N terminus may limit its affinity for β-lactams. Sequence comparisons identify Rm3-like MBLs in numerous other environmental samples and species. Our data suggest that Rm3-like enzymes represent a distinct group of B3 MBLs with a wide distribution and can be considered an environmental reservoir of determinants of β-lactam resistance.

PubMed: 27431213
DOI: 10.1128/AAC.00750-16

実験手法

X-RAY DIFFRACTION (1.75 Å)