Lipopeptide antibiotics disrupt interactions of undecaprenyl phosphate with UptA.

ABSTRACT: The peptidoglycan pathway represents one of the most successful antibacterial targets with the last critical step being the flipping of carrier lipid, undecaprenyl phosphate (C₅₅-P), across the membrane to reenter the pathway. This translocation of C₅₅-P is facilitated by DedA and DUF368 domain-containing family membrane proteins via unknown mechanisms. Here, we employ native mass spectrometry to investigate the interactions of UptA, a member of the DedA family of membrane protein from Bacillus subtilis, with C₅₅-P, membrane phospholipids, and cell wall-targeting antibiotics. Our results show that UptA, expressed and purified in Escherichia coli, forms monomer-dimer equilibria, and binds to C₅₅-P in a pH-dependent fashion. Specifica

SUBMITTER: Oluwole AO 

PROVIDER: S-EPMC11474028 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature