Mechanism of action of a boron-dependent antibiotic entails synergistic binding.

ABSTRACT: Laspartomycin C (LspC) is a calcium-dependent antibiotic (CDA), a family of peptide antibiotics that has an intriguing mechanism of action (MOA) and great promise in drug development. While it has long been known that CDAs require Ca(ii) to function, the mechanistic details remain elusive. We previously reported a synthetic analog of LspC, termed B1, that can be fully activated by phenylboronic acid (PBA) and is no longer dependent upon Ca(ii) for its antibacterial activity, providing a new entry point to study the MOA of CDAs. In other words, Ca(ii) is the cofactor for LspC activation and PBA is the cofactor for B1 activation. Presented herein is their thorough characterization using isothermal calorimetry, NMR, and molecular dynamics simulation. To our surprise, we found that even though

SUBMITTER: Chiou SL 

PROVIDER: S-EPMC12821149 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature