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dc.contributor.authorMann, Greg
dc.contributor.authorHuo, Liujie
dc.contributor.authorAdam, Sebastian
dc.contributor.authorNardone, Brunello
dc.contributor.authorVendome, Jeremie
dc.contributor.authorWestwood, Nicholas James
dc.contributor.authorMüller, Rolf
dc.contributor.authorKoehnke, Jesko
dc.identifier.citationMann , 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 .
dc.identifier.otherPURE: 246458685
dc.identifier.otherPURE UUID: 20897e36-a178-4354-a761-d4de02f39c73
dc.identifier.otherScopus: 84995575932
dc.identifier.otherORCID: /0000-0003-0630-0138/work/56424155
dc.identifier.otherWOS: 000392932200012
dc.descriptionJK 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).en
dc.description.abstractThe 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.
dc.rights© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. This work has been made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at:
dc.subjectLeucyl-amino peptidaseen
dc.subjectQD Chemistryen
dc.titleStructure and substrate recognition of the Bottromycin maturation enzyme BotPen
dc.typeJournal articleen
dc.contributor.sponsorEuropean Research Councilen
dc.contributor.institutionUniversity of St Andrews. School of Chemistryen
dc.contributor.institutionUniversity of St Andrews. EaSTCHEMen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.description.statusPeer revieweden

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