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Bonanno, Jeffrey B.

Publications and source records attributed to Bonanno, Jeffrey B..

3 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Structures of FOX-4 Cephamycinase in Complex with Transition-State Analog Inhibitors

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 IC 50 value < 0.1 μM. Our analyses open up new opportunities for the design of novel transition-state analogs of class C enzymes.

59 BASIC BIOLOGICAL SCIENCES↗