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Structure and substrate recognition of the Bottromycin maturation enzyme BotP
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dc.contributor.author | Mann, Greg | |
dc.contributor.author | Huo, Liujie | |
dc.contributor.author | Adam, Sebastian | |
dc.contributor.author | Nardone, Brunello | |
dc.contributor.author | Vendome, Jeremie | |
dc.contributor.author | Westwood, Nicholas James | |
dc.contributor.author | Müller, Rolf | |
dc.contributor.author | Koehnke, Jesko | |
dc.date.accessioned | 2017-09-21T23:32:03Z | |
dc.date.available | 2017-09-21T23:32:03Z | |
dc.date.issued | 2016-12-02 | |
dc.identifier | 246458685 | |
dc.identifier | 20897e36-a178-4354-a761-d4de02f39c73 | |
dc.identifier | 84995575932 | |
dc.identifier | 000392932200012 | |
dc.identifier.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 | en |
dc.identifier.issn | 1439-4227 | |
dc.identifier.other | ORCID: /0000-0003-0630-0138/work/56424155 | |
dc.identifier.uri | https://hdl.handle.net/10023/11711 | |
dc.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). | en |
dc.description.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. | |
dc.format.extent | 7 | |
dc.format.extent | 2066272 | |
dc.language.iso | eng | |
dc.relation.ispartof | ChemBioChem | en |
dc.subject | Bottromycin | en |
dc.subject | Leucyl-amino peptidase | en |
dc.subject | RiPPs | en |
dc.subject | BotP | en |
dc.subject | Biosynthesis | en |
dc.subject | QD Chemistry | en |
dc.subject | NDAS | en |
dc.subject.lcc | QD | en |
dc.title | Structure and substrate recognition of the Bottromycin maturation enzyme BotP | en |
dc.type | Journal article | en |
dc.contributor.sponsor | European Research Council | en |
dc.contributor.institution | University of St Andrews. School of Chemistry | en |
dc.contributor.institution | University of St Andrews. EaSTCHEM | en |
dc.contributor.institution | University of St Andrews. Biomedical Sciences Research Complex | en |
dc.identifier.doi | 10.1002/cbic.201600406 | |
dc.description.status | Peer reviewed | en |
dc.date.embargoedUntil | 2017-09-21 | |
dc.identifier.url | http://onlinelibrary.wiley.com/wol1/doi/10.1002/cbic.201600406/suppinfo | en |
dc.identifier.grantnumber | NCB-TNT | en |
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