Unraveling the mechanism of small molecule induced activation of Staphylococcus aureus signal peptidase IB.

ABSTRACT: Staphylococcus aureus signal peptidase IB (SpsB) is an essential enzyme for protein secretion. While inhibition of its activity by small molecules is a well-precedented mechanism to kill bacteria, the mode of activation is however less understood. We here investigate the activation mechanism of a recently introduced activator, the antibiotic compound PK150, and demonstrate by combined experimental and Molecular Dynamics (MD) simulation studies a unique principle of enzyme stimulation. Mass spectrometric studies with an affinity-based probe of PK150 unravel the binding site of PK150 in SpsB which is used as a starting point for MD simulations. Our model shows the localization of the molecule in an allosteric pocket next to the active site which shields the catalytic dyad from excess water t

SUBMITTER: Chen SY 

PROVIDER: S-EPMC11266668 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature