Probing substrate recognition of bacterial lipoprotein signal peptidase using FRET reporters

Seiya Kitamura, Dennis W. Wolan

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Lipoprotein signal peptidase (Lsp) is a transmembrane aspartic acid protease with a pivotal role in the bacterial lipoprotein maturation pathway. Despite the universal use of Lsp across the Bacterial Kingdom and its potential as an antibiotic target, the substrate recognition patterns of Lsp are poorly understood. Here, we investigated the substrate recognition and biochemical properties of Lsp from Gram (Escherichia coli) and Gram+ (Streptococcus pyogenes) bacteria, using synthetic peptide-based FRET reporters. Didecanoyl glycerol was found to be an optimal lipid length, and Lsp demonstrated exclusive enantio-selectivity for the (R)-form of the diacylglycerol. Our study will facilitate the iterative optimization of in vitro Lsp assays, as well as provide the first chemical interrogation into the substrate scope of Lsp.

Original languageEnglish (US)
Pages (from-to)2289-2296
Number of pages8
JournalFEBS Letters
Issue number13
StatePublished - Jul 2018
Externally publishedYes


  • enzyme kinetics
  • FRET substrate
  • lipidated peptide
  • lipoprotein signal peptidase
  • membrane protease

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology


Dive into the research topics of 'Probing substrate recognition of bacterial lipoprotein signal peptidase using FRET reporters'. Together they form a unique fingerprint.

Cite this