Bath 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

β-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 β-lactamase enzymes, of which there are four major classes (A, B, C, and D).  Carbapenems are a newer class of β-lactams that are meant to be β-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 β-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 β-lactamase/imipenem complexes provides insight on the ability of CHDLs to hydrolyze carbapenems.

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

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