5iqk
Rm3 metallo-beta-lactamase
Structural highlights
FunctionPublication Abstract from PubMedbeta-Lactamase production increasingly threatens the effectiveness of beta-lactams, which remain a mainstay of antimicrobial chemotherapy. New activities emerge both through mutation of previously known beta-lactamases and mobilization from environmental reservoirs. The spread of metallo-beta-lactamases (MBLs) represents a particular challenge through their typically broad spectrum activities, encompassing carbapenems in addition to other beta-lactam classes. Increasingly, genomic and metagenomic studies reveal distribution of putative MBLs in the environment, but in most cases their activity against clinically relevant beta-lactams, and hence the extent to which they can be considered a resistance reservoir, remains uncharacterized. Here we characterize the product of one such gene, blaRm3, identified through functional metagenomic sampling of an environment with high biocide exposure. blaRm3 encodes a subclass B3 MBL that, when expressed in recombinant E. coli, 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 alphabeta/betaalpha fold, which more closely resembles mobilized B3 MBLs (AIM-1, 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 beta-lactam affinity. 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 as an environmental reservoir of beta-lactam resistance. Structural and Biochemical Characterization of Rm3, a SubClass B3 Metallo-beta-Lactamase Identified from a Functional Metagenomic Study.,Salimraj R, Zhang L, Hinchliffe P, Wellington EM, Brem J, Schofield CJ, Gaze WH, Spencer J Antimicrob Agents Chemother. 2016 Jul 18. pii: AAC.00750-16. PMID:27431213[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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