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dc.contributor.authorYang, Jianhong
dc.contributor.authorWang, Yuxi
dc.contributor.authorWang, Taijing
dc.contributor.authorJiang, Jian
dc.contributor.authorBotting, Catherine Helen
dc.contributor.authorLiu, Huanting
dc.contributor.authorChen, Qiang
dc.contributor.authorYang, Jingliang
dc.contributor.authorNaismith, James Henderson
dc.contributor.authorZhu, Xiaofeng
dc.contributor.authorChen, Lijuan
dc.date.accessioned2016-07-15T14:30:05Z
dc.date.available2016-07-15T14:30:05Z
dc.date.issued2016-06-30
dc.identifier.citationYang , J , Wang , Y , Wang , T , Jiang , J , Botting , C H , Liu , H , Chen , Q , Yang , J , Naismith , J H , Zhu , X & Chen , L 2016 , ' Pironetin reacts covalently with cysteine-316 of α-tubulin to destabilize microtubule ' Nature Communications , vol. 7 , 12103 . https://doi.org/10.1038/ncomms12103en
dc.identifier.issn2041-1723
dc.identifier.otherPURE: 243135377
dc.identifier.otherPURE UUID: 545ca2ea-1a9b-4f98-b6e1-71c6a6dfa70c
dc.identifier.otherScopus: 84977097910
dc.identifier.urihttp://hdl.handle.net/10023/9149
dc.descriptionThis work was funded by grants to C.L. from the National Natural Science Foundation of 
China (81373283 and U1402222). J.H.N. is supported as an award holder of Chinese National 
Thousand Talents Program, Wellcome Trust Senior Investigator Award (WT100209MA) and 
Royal Society Wolfson Merit Award. X.Z. is supported by Sichuan Province Thousand Talents 
Scheme in China and the State Key Program of National Natural Science of China (21534008).en
dc.description.abstractMolecules which alter the normal dynamics of microtubule assembly and disassembly 
include many anticancer drugs in clinical use. So far all such therapeutics target β-tubulin 
and structural biology has explained the basis of their action and permitted design of new 
drugs. However by shifting the profile of β-tubulin isoforms, cancer cells become resistant to 
treatment. Compounds that bind to α-tubulin are less well characterized and unexploited. 
The natural product pironetin is known to bind to α-tubulin and is a potent inhibitor of 
microtubule polymerization. Previous reports had identified that pironetin reacts with lysine-352 
residue however analogues designed on this model had much lower potency which was 
difficult to explain, hindering further development. We report crystallographic and mass 
spectrometric data that reveal that pironetin forms a covalent bond to cysteine-316 in α-tubulin 
via a Michael addition reaction. These data provide a basis for the rational design of α-tubulin targeting chemotherapeutics. 

dc.format.extent9
dc.language.isoeng
dc.relation.ispartofNature Communicationsen
dc.rights© The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.en
dc.subjectQD Chemistryen
dc.subjectDASen
dc.subject.lccQDen
dc.titlePironetin reacts covalently with cysteine-316 of α-tubulin to destabilize microtubuleen
dc.typeJournal articleen
dc.description.versionPostprinten
dc.description.versionPublisher PDFen
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.identifier.doihttps://doi.org/10.1038/ncomms12103
dc.description.statusPeer revieweden


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