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Beth Vallier ACF Abstract FY12

"Structure determination and analysis of the class D carbapenemase OXA-24 in complex imipenem"

243rd American Chemical Society (ACS) Spring 2012 National Meeting

²-lactams are the most widely prescribed class of antibiotics, but their utility is compromised due to resistance. The leading cause of resistance is the expression of ²-lactamase enzymes, of which there are four major classes (A, B, C, and D). Carbapenems are a newer class of ²-lactams that are meant to be ²-lactamase resistant. Particularly worrisome is the emergence of subclasses of the class D enzymes that exhibit carbapenemase activity. OXA-24 is one example of these carbapenem hydrolyzing Class D ²-lactamases, or CHDLs. Using a deacylation deficient mutant of OXA-24 (Lys84Asp), the structure of the acyl-enzyme complex with the carbapenem imipenem was determined to 1.94 Å resolution. Comparison with other ²-lactamase/imipenem complexes provides insight on the ability of CHDLs to hydrolyze carbapenems.

Beth C. Vallier, David A. Leonard, and Rachel A. Powers