5b3r

Publication Abstract from PubMed

IMP-type metallo-beta-lactamases (MBLs) are exogenous zinc metalloenzymes that hydrolyze a broad range of beta-lactams, including carbapenems. Here we report the crystal structure of IMP-18, an MBL cloned from Pseudomonas aeruginosa, at 2.0-A resolution. The overall structure of IMP-18 resembles that of IMP-1, with an alphabeta/betaalpha "folded sandwich" configuration, but the loop that covers the active site has a distinct conformation. The relationship between IMP-18's loop conformation and its kinetic properties was investigated by replacing the amino acid residues that can affect the loop conformation (Lys44, Thr50, and Ile69) in IMP-18 with those occupying the corresponding positions in the well-described enzyme IMP-1. The replacement of Thr50 with Pro considerably modified IMP-18's kinetic properties, specifically those pertaining to meropenem, with the kcat/Km value increased by an order of magnitude. The results indicate that this is a key residue that defines the kinetic properties of IMP-type beta-lactamases.

Structural and Mutagenic Analysis of Metallo-beta-Lactamase IMP-18.,Furuyama T, Nonomura H, Ishii Y, Hanson ND, Shimizu-Ibuka A Antimicrob Agents Chemother. 2016 Aug 22;60(9):5521-6. doi: 10.1128/AAC.00985-16., Print 2016 Sep. PMID:27381398^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.