biostudies-literaturePrester ABundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)Bundesministerium für Bildung und ForschungDeutsche ForschungsgemeinschaftDeutsche Forschungsgemeinschaft (German Research Foundation)Joachim Herz StiftungJoachim Herz Stiftung (Joachim Herz Foundation)152https://www.ebi.ac.uk/biostudies/studies/S-EPMC11226702biostudies-literatureUnknown7(1)The emergence and spread of antibiotic resistance represent a growing threat to public health. Of particular concern is the appearance of β-lactamases, which are capable to hydrolyze and inactivate the most important class of antibiotics, the β-lactams. Effective β-lactamase inhibitors and mechanistic insights into their action are central in overcoming this type of resistance, and in this context boronate-based β-lactamase inhibitors were just recently approved to treat multidrug-resistant bacteria. Using boric acid as a simplified inhibitor model, time-resolved serial crystallography was employed to obtain mechanistic insights into binding to the active site serine of β-lactamase CTX-M-14, identifying a reaction time frame of 80-100 ms. In a next step, the subsequent 1,2-diol boric esterCommunications chemistryTime-resolved crystallography of boric acid binding to the active site serine of the β-lactamase CTX-M-14 and subsequent 1,2-diol esterification.PMC1122670205K19GU405K20GUB390715994Infecto-physicsChapman HWerner NAepfelbacher MRohde HHakanpaa JBetzel CMeyer JPerbandt MHenkel AHinrichs WOberthuer DYefanov OPompidor GMaracke JPrester AGalchenkova MfalseTime-resolved crystallography of boric acid binding to the active site serine of the β-lactamase CTX-M-14 and subsequent 1,2-diol esterification.The emergence and spread of antibiotic resistance represent a growing threat to public health. Of particular concern is the appearance of β-lactamases, which are capable to hydrolyze and inactivate the most important class of antibiotics, the β-lactams. Effective β-lactamase inhibitors and mechanistic insights into their action are central in overcoming this type of resistance, and in this context boronate-based β-lactamase inhibitors were just recently approved to treat multidrug-resistant bacteria. Using boric acid as a simplified inhibitor model, time-resolved serial crystallography was employed to obtain mechanistic insights into binding to the active site serine of β-lactamase CTX-M-14, identifying a reaction time frame of 80-100 ms. In a next step, the subsequent 1,2-diol boric ester2024-01-01T00:00:00Z2024 Jul2026-05-29T09:39:35.481Z2024-11-20T23:50:09.031ZS-EPMC112267023896971810.1038/s42004-024-01236-w