Conformational dynamics of the membrane enzyme LspA upon antibiotic and substrate binding.

ABSTRACT: Lipoprotein signal peptidase (LspA) is an aspartyl protease that cleaves the transmembrane helix signal peptide of lipoproteins as part of the lipoprotein-processing pathway. Members of this pathway are excellent targets for the development of antibiotic therapeutics because they are essential in Gram-negative bacteria, are important for virulence in Gram-positive bacteria, and may not develop antibiotic resistance. Here, we report the conformational dynamics of LspA in the apo state and bound to the antibiotic globomycin determined using molecular dynamics simulations and electron paramagnetic resonance. The periplasmic helix fluctuates on the nanosecond timescale and samples unique conformations in the different states. In the apo state, the dominant conformation is the most closed and o

SUBMITTER: Caldwell TA 

PROVIDER: S-EPMC9247476 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature