@article{dc4403dd395d4b73b74c9ea72603f816,
title = "Structures of FOX-4 cephamycinase in complex with transition-state analog inhibitors",
abstract = "Boronic acid transition-state analog inhibitors (BATSIs) are partners with β-lactam antibiotics for the treatment of complex bacterial infections. Herein, microbiological, biochemical, and structural findings on four BATSIs with the FOX-4 cephamycinase, a class C β-lactamase that rapidly hydrolyzes cefoxitin, are revealed. FOX-4 is an extended-spectrum class C cephalosporinase that demonstrates conformational flexibility when complexed with certain ligands. Like other β-lactamases of this class, studies on FOX-4 reveal important insights into structure–activity relationships. We show that SM23, a BATSI, shows both remarkable flexibility and affinity, binding similarly to other β-lactamases, yet retaining an IC50 value < 0.1 μM. Our analyses open up new opportunities for the design of novel transition-state analogs of class C enzymes.",
keywords = "Boronic acid, Cephamycinase, Transition-state analog inhibitor, β-lactam, β-lactamase",
author = "Lefurgy, {Scott T.} and Emilia Caselli and Taracila, {Magdalena A.} and Malashkevich, {Vladimir N.} and Beena Biju and Papp-Wallace, {Krisztina M.} and Bonanno, {Jeffrey B.} and Fabio Prati and Almo, {Steven C.} and Bonomo, {Robert A.}",
note = "Funding Information: Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH) to R.A.B. under award numbers R01AI100560, R01AI063517, and R01AI072219. This study was also supported in part by funds and/or facilities provided by the Cleveland Department of Veterans Affairs, award numbers 1I01BX002872 to K.M.P.-W. and 1I01BX001974 to R.A.B. 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. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Department of Veterans Affairs. S.T.L. is supported by a Hofstra Faculty Research & Development Grant. The Einstein Crystallographic Core facility is supported by NIH grants P30 CA013330 and S10 OD020068. Funding Information: Funding: Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH) to R.A.B. under award numbers R01AI100560, R01AI063517, and R01AI072219. This study was also supported in part by funds and/or facilities provided by the Cleveland Department of Veterans Affairs, award numbers 1I01BX002872 to K.M.P.-W. and 1I01BX001974 to R.A.B. 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. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Department of Veterans Affairs. S.T.L. is supported by a Hofstra Faculty Research & Development Grant. The Einstein Crystallographic Core facility is supported by NIH grants P30 CA013330 and S10 OD020068. Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2020",
month = may,
doi = "10.3390/biom10050671",
language = "English (US)",
volume = "10",
journal = "Biomolecules",
issn = "2218-273X",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "5",
}