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Merck

Biochemical characterization of IMP-30, a metallo-ฮฒ-lactamase with enhanced activity toward ceftazidime.

Antimicrobial agents and chemotherapy (2013-07-10)
Kevin M Pegg, Eleanor M Liu, Alecander E Lacuran, Peter Oelschlaeger
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IMP-type enzymes constitute a clinically important family of metallo-ฮฒ-lactamases that has grown dramatically in the past decade to its current 45 known members. Here, we report the biochemical characterization of IMP-30 in comparison to IMP-1, from which it deviates by a single E59K mutation. Kinetics, MIC assays, docking, and molecular dynamics simulations support a scenario in which Lys59 interacts with the ceftazidime R1 group, resulting in increased water access and enhanced turnover and MIC of ceftazidime.

MATERIALS
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Ceftazidime, European Pharmacopoeia (EP) Reference Standard
USP
Ceftazidime pentahydrate, United States Pharmacopeia (USP) Reference Standard
Ceftazidime for peak identification, European Pharmacopoeia (EP) Reference Standard