Download MendeleyStructure and Substrate Recognition of the Bottromycin Maturation Enzyme BotP.
Mann, G., Huo, L., Adam, S., Nardone, B., Vendome, J., Westwood, N.J., Muller, R., Koehnke, J.(2016) Chembiochem 17: 2286-2292
- PubMed: 27653442
- DOI: https://doi.org/10.1002/cbic.201600406
- Primary Citation of Related Structures:
5LHJ, 5LHK - PubMed Abstract:
The bottromycins are a family of highly modified peptide natural products, which display potent antimicrobial activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Bottromycins have recently been shown to be ribosomally synthesized and post-translationally modified peptides (RiPPs). Unique amongst RiPPs, the precursor peptide BotA contains a C-terminal "follower" sequence, rather than the canonical N-terminal "leader" sequence. We report herein the structural and biochemical characterization of BotP, a leucyl-aminopeptidase-like enzyme from the bottromycin pathway. We demonstrate that BotP is responsible for the removal of the N-terminal methionine from the precursor peptide. Determining the crystal structures of both apo BotP and BotP in complex with Mn 2+ allowed us to model a BotP/substrate complex and to rationalize substrate recognition. Our data represent the first step towards targeted compound modification to unlock the full antibiotic potential of bottro- mycin.
Organizational Affiliation:
School of Chemistry and Biomedical Sciences Research Centre, University of St. Andrews, North Haugh, St. Andrews, KY16 9ST, UK.
