Phosphorylation of Staphylococcus aureus β-lactamase, a prerequisite to its sequestration on the cytoplasmic membrane.

ABSTRACT: Approximately 50% of the class A Staphylococcus aureus β-lactamase (BlaZ) is secreted to the milieu as a resistance vanguard against β-lactam antibiotics. We disclose that the remaining 50% of the β-lactamase is sequestered on the surface of the cytoplasmic membrane in a process that involves its lipidation and phosphorylation, with lipidation being a prerequisite for phosphorylation. Lipidation of a cysteine in the lipobox of BlaZ is ensued by more than one phosphorylation event and cleavage of the signal peptide by a type II signal peptidase. The membrane-bound β-lactamase retains catalytic activity in the turnover of β-lactam antibiotics. A combination of mass-spectrometric analysis and site-directed mutagenesis identified eight sites for phosphorylation. Phosphorylation on Y34, Y41, T1

SUBMITTER: Kim C 

PROVIDER: S-EPMC12432424 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature