The X‐ray crystal structure of the Acinetobacter‐Derived Cephalosporinase, ADC‐7, at 1.7 Å

Abstract

β‐Lactam resistance in Acinetobacter baumannii presents one of the greatest challenges to contemporary antimicrobial chemotherapy. The Acinetobacter‐Derived Cephalosporinases (ADCs) are class C β‐lactamases found in A. baumannii and other Acinetobacter species that are responsible for resistance to penicillins, cephalosporins, and β‐lactam‐β‐lactamase inhibitor combinations. In order to probe the mechanism of substrate turnover, as well as to design novel β‐lactam antibiotics, it was important to elucidate the protein structure of an ADC enzyme. Here, we report the successful purification, crystallization, and determination of the crystal structure of ADC‐7 at 1.7 Å. This complete structure allows for the critical comparison of the overall structure and active site architecture of ADC‐7 with the known cephalosporinase, AmpC. Hopefully, our work will contribute to the development of a structure/function relationship for ADC‐7 that will provide insight into bacterial antibiotic resistance.