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Structure and substrate recognition of the Bottromycin maturation enzyme BotP

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Westwood_2016_CBC_Structure_AAM.pdf (1.970Mb)
Date
02/12/2016
Author
Mann, Greg
Huo, Liujie
Adam, Sebastian
Nardone, Brunello
Vendome, Jeremie
Westwood, Nicholas James
Müller, Rolf
Koehnke, Jesko
Funder
European Research Council
Grant ID
NCB-TNT
Keywords
Bottromycin
Leucyl-amino peptidase
RiPPs
BotP
Biosynthesis
QD Chemistry
NDAS
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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
DOI
https://doi.org/10.1002/cbic.201600406
ISSN
1439-4227
Type
Journal article
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: https://doi.org/10.1002/cbic.201600406
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).
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  • University of St Andrews Research
URL
http://onlinelibrary.wiley.com/wol1/doi/10.1002/cbic.201600406/suppinfo
URI
http://hdl.handle.net/10023/11711

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