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dc.contributor.authorKoehnke, Jesko Alexander Johannes Gunter
dc.contributor.authorMann, Greg
dc.contributor.authorBent, Andrew Frank
dc.contributor.authorLudewig, Hannes
dc.contributor.authorShirran, Sally Lorna
dc.contributor.authorBotting, Catherine Helen
dc.contributor.authorLebl, Tomas
dc.contributor.authorHoussen, Wael
dc.contributor.authorJaspers, Marcel
dc.contributor.authorNaismith, Jim
dc.date.accessioned2016-12-23T00:32:15Z
dc.date.available2016-12-23T00:32:15Z
dc.date.issued2015-08
dc.identifier.citationKoehnke , J A J G , Mann , G , Bent , A F , Ludewig , H , Shirran , S L , Botting , C H , Lebl , T , Houssen , W , Jaspers , M & Naismith , J 2015 , ' Structural analysis of leader peptide binding enables leader-free cyanobactin processing ' , Nature Chemical Biology , vol. 11 , no. 8 , pp. 558-563 . https://doi.org/10.1038/nchembio.1841en
dc.identifier.issn1552-4450
dc.identifier.otherPURE: 181016894
dc.identifier.otherPURE UUID: be4cb5fc-bc51-4e7d-ad30-eee1ebd0fce5
dc.identifier.otherScopus: 84937395423
dc.identifier.otherORCID: /0000-0002-0269-3221/work/48131691
dc.identifier.otherORCID: /0000-0003-3516-3507/work/32169109
dc.identifier.otherWOS: 000358255300009
dc.identifier.urihttp://hdl.handle.net/10023/10008
dc.descriptionThis work was supported by grants from the ERC 339367 (J.H.N. and M.J.) and BBSRC BB/K015508/1 (J.H.N and M.J.). We acknowledge use of the Diamond (beamlines I02 and I24) and ESRF (beamline ID29) synchrotrons. JHN is Royal Society Wolfson Merit Award Holder and a 1000 talent scholar of the Chinese Government at Sichuan University.en
dc.description.abstractRegioselective modification of amino acids within the context of a peptide is common to a number of biosynthetic pathways, and many of the resulting products have potential as therapeutics. The ATP-dependent enzyme LynD heterocyclizes multiple cysteine residues to thiazolines within a peptide substrate. The enzyme requires the substrate to have a conserved N-terminal leader for full activity. Catalysis is almost insensitive to immediately flanking residues in the substrate, suggesting that recognition occurs distant from the active site. Nucleotide and peptide substrate co-complex structures of LynD reveal that the substrate leader peptide binds to and extends the β-sheet of a conserved domain of LynD, whereas catalysis is accomplished in another conserved domain. The spatial segregation of catalysis from recognition combines seemingly contradictory properties of regioselectivity and promiscuity, and it appears to be a conserved strategy in other peptide-modifying enzymes. A variant of LynD that efficiently processes substrates without a leader peptide has been engineered.
dc.format.extent8
dc.language.isoeng
dc.relation.ispartofNature Chemical Biologyen
dc.rights© 2014. Macmillan Publishers Limited. All rights reserved. NPG Terms of reuse of archived manuscipts applies http://www.nature.com/authors/policies/license.htmlen
dc.subjectQD Chemistryen
dc.subjectNDASen
dc.subjectBDCen
dc.subjectR2Cen
dc.subject.lccQDen
dc.titleStructural analysis of leader peptide binding enables leader-free cyanobactin processingen
dc.typeJournal articleen
dc.contributor.sponsorBBSRCen
dc.description.versionPostprinten
dc.contributor.institutionUniversity of St Andrews. School of Chemistryen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.contributor.institutionUniversity of St Andrews. EaSTCHEMen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.1038/nchembio.1841
dc.description.statusPeer revieweden
dc.date.embargoedUntil2016-12-22
dc.identifier.grantnumberBB/K015508/1en


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