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dc.contributor.authorHarding, Christopher John
dc.contributor.authorSutherland, Emmajay
dc.contributor.authorHanna, Jane
dc.contributor.authorHouston, Douglas
dc.contributor.authorMelo Czekster, Clarissa
dc.date.accessioned2021-01-18T12:30:06Z
dc.date.available2021-01-18T12:30:06Z
dc.date.issued2021-01-15
dc.identifier.citationHarding , C J , Sutherland , E , Hanna , J , Houston , D & Melo Czekster , C 2021 , ' Bypassing the requirement for aminoacyl-tRNA by a cyclodipeptide synthase enzyme ' , RSC Chemical Biology , vol. Advance article . https://doi.org/10.1039/D0CB00142Ben
dc.identifier.issn2633-0679
dc.identifier.otherPURE: 272209192
dc.identifier.otherPURE UUID: cf538f15-c1df-49fe-8496-890e0347064f
dc.identifier.otherORCID: /0000-0002-7163-4057/work/87404245
dc.identifier.otherWOS: 000621052100015
dc.identifier.otherScopus: 85116067119
dc.identifier.urihttps://hdl.handle.net/10023/21283
dc.descriptionC. J. H. and C. M. C. are funded by the Wellcome trust (210486/Z/18/Z), ES is funded by the Cunningham trust (PhD-CT-18-41).en
dc.description.abstractCyclodipeptide synthases (CDPSs) produce a variety of cyclic dipeptide products by utilising two aminoacylated tRNA substrates. We sought to investigate the minimal requirements for substrate usage in this class of enzymes as the relationship between CDPSs and their substrates remains elusive. Here, we investigated the Bacillus thermoamylovorans enzyme, BtCDPS, which synthesises cyclo(L-Leu–L-Leu). We systematically tested where specificity arises and, in the process, uncovered small molecules (activated amino esters) that will suffice as substrates, although catalytically poor. We solved the structure of BtCDPS to 1.7 Å and combining crystallography, enzymatic assays and substrate docking experiments propose a model for how the minimal substrates interact with the enzyme. This work is the first report of a CDPS enzyme utilizing a molecule other than aa-tRNA as a substrate; providing insights into substrate requirements and setting the stage for the design of improved simpler substrates.
dc.format.extent11
dc.language.isoeng
dc.relation.ispartofRSC Chemical Biologyen
dc.rightsCopyright © 2021 The Author(s). Open Access. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.en
dc.subjectQH301 Biologyen
dc.subjectDASen
dc.subject.lccQH301en
dc.titleBypassing the requirement for aminoacyl-tRNA by a cyclodipeptide synthase enzymeen
dc.typeJournal articleen
dc.contributor.sponsorCunningham Trusten
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.1039/D0CB00142B
dc.description.statusPeer revieweden
dc.identifier.grantnumberen


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