Structural highlights
Publication Abstract from PubMedBoronic acid transition-state analog inhibitors (BATSIs) are partners with beta-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 beta-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 beta-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 beta-lactamases, yet retaining an IC50 value < 0.1 muM. Our analyses open up new opportunities for the design of novel transition-state analogs of class C enzymes. Structures of FOX-4 Cephamycinase in Complex with Transition-State Analog Inhibitors.,Lefurgy ST, Caselli E, Taracila MA, Malashkevich VN, Biju B, Papp-Wallace KM, Bonanno JB, Prati F, Almo SC, Bonomo RA Biomolecules. 2020 Apr 27;10(5). pii: biom10050671. doi: 10.3390/biom10050671. PMID:32349291[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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