ADC-7, beta-lactamase, infectious disease, antibiotic resistance, enzyme, kinetics, x-ray crystallography, protein structure, inhibitor, BATSI, Acinetobacter baumannii
Amino Acids, Peptides, and Proteins | Biochemistry | Enzymes and Coenzymes | Medicinal and Pharmaceutical Chemistry | Medicinal-Pharmaceutical Chemistry | Molecular Biology
Swanson, Hollister C.; Powers, Rachel; and Wallar, Bradley, "Identification of a Potent Inhibitor for the Extended Spectrum Class C Beta-Lactamase, ADC-7" (2013). Student Summer Scholars. 97.
Resistance to b-lactam antibiotics in the pathogenic bacteria, Acinetobacter baumannii, presents one of the greatest challenges to current antimicrobial chemotherapy. Majority of resistance is due to expression of class C β-lactamase enzymes, known as Acinetobacter-Derived Cephalosporinases (ADCs). The enzyme ADC-7 is a broad-spectrum class C b-lactamase, capable of deactivating multiple types of antibiotics. Boronic acid transition state inhibitors (BATSIs) are compounds that bind covalently and reversibly to class C b-lactamases. Enzyme kinetic studies of one BATSI, designated S02030, demonstrated a greater affinity for binding than a common cephalosporin substrate. After expression and purification of ADC-7, the first known X-ray crystal structure of ADC-7 with inhibitor complex was solved at 2.03 Å resolution. The ADC-7/S02030 complex provides insight into ADC enzyme structure and offers a novel starting point for the structure-based optimization of b-lactamase inhibitors.