Abstract
The ever-increasing occurrence of antibiotic resistance presents a major threat to public health. Specifically, resistance conferred by β-lactamases places the efficacy of currently available antibiotics at risk. Klebsiella pneumoniae carbapenemase-2 (KPC-2) is a β-lactamase that enables carbapenem resistance and represents a clear and present danger to global public health. In order to combat bacterial infections harboring KPC-2 expression, inhibitors with improved potency need to be developed. Although the structure of KPC-2 has been solved by X-ray crystallography, NMR provides the unique opportunity to study the structure and dynamics of flexible loop regions in solution. Here we report the 1H, 13C, and 15N backbone chemical shift assignments for KPC-2 in the apo state as the first step towards the study of KPC-2 dynamics in the presence and absence of ligands to enable the rational design of optimized inhibitors.
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Acknowledgements
The authors acknowledge financial support from the National Institutes of Health through the National Institute of General Medical Sciences under Award Number R35GM128595 to RCP and through the National Institute of Allergy and Infectious Diseases under Award Numbers R01AI100560, R01AI063517, R21AI114508, and R01AI072219 to RAB. This study was supported in part by funds and/or facilities provided by the Cleveland Department of Veterans Affairs, Award Number 1I01BX001974 to RAB from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development and the Geriatric Research Education and Clinical Center VISN 10 to RAB. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Veterans Affairs. MALDI-TOF data were collected using instrumentation purchased with NSF grant award CHE0839233. The authors acknowledge institutional support from Miami University through the Robert H. and Nancy J. Blayney Professorship to RCP.
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The corresponding author (RCP) is the recipient of a research contract from Allecra Therapeutics to study KPC-2. The authors RCP and RAB are the co-recipients of a research contract (MISP #57394) from Merck & Co. to study inhibition of KPC-2.
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VanPelt, J., Shurina, B.A., Ramelot, T.A. et al. 1H, 13C, and 15N backbone resonance assignments for KPC-2, a class A serine-β-lactamase. Biomol NMR Assign 13, 139–142 (2019). https://doi.org/10.1007/s12104-018-9866-8
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DOI: https://doi.org/10.1007/s12104-018-9866-8