Structure and substrate recognition of the Bottromycin maturation enzyme BotP
Abstract
The bottromycins are a family of highly modified peptide natural products displaying potent antimicrobial activity against Gram-positive bacteria including methicillin-resistant Staphyloccoccus 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 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 apo BotP and of BotP in complex with Mn2+ 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 bottromycin.
Citation
Mann , G , Huo , L , Adam , S , Nardone , B , Vendome , J , Westwood , N J , Müller , R & Koehnke , J 2016 , ' Structure and substrate recognition of the Bottromycin maturation enzyme BotP ' , ChemBioChem , vol. 17 , no. 23 , pp. 2286-2292 . https://doi.org/10.1002/cbic.201600406
Publication
ChemBioChem
Status
Peer reviewed
ISSN
1439-4227Type
Journal article
Description
JK would like to thank the University of St Andrews, which is supported by a Wellcome Trust Capital Award (086036) and the Deutsche Forschungsgemeinschaft for an Emmy Noether fellowship (KO4116/3-1). BN would like to thank the European Research Council (339367).Collections
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