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dc.contributor.authorMartínez-Sáez, Nuria
dc.contributor.authorCastro-López, Jorge
dc.contributor.authorValero-González, Jessika
dc.contributor.authorMadariaga, David
dc.contributor.authorCompañón, Ismael
dc.contributor.authorSomovilla, Víctor J
dc.contributor.authorSalvadó, Míriam
dc.contributor.authorAsensio, Juan L
dc.contributor.authorJiménez-Barbero, Jesús
dc.contributor.authorAvenoza, Alberto
dc.contributor.authorBusto, Jesús H
dc.contributor.authorLopes Bernardes, Goncalo
dc.contributor.authorPeregrina, Jesús M
dc.contributor.authorHurtado-Guerrero, Ramón
dc.contributor.authorCorzana, Francisco
dc.date.accessioned2015-08-28T13:23:53Z
dc.date.available2015-08-28T13:23:53Z
dc.date.issued2015-08-17
dc.identifier.citationAngewandte Chemie International Edition Volume 54, Issue 34, pages 9830–9834, August 17, 2015. DOI: 10.1002/anie.201502813
dc.identifier.issn1433-7851
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/250402
dc.description.abstractThe structural features of MUC1-like glycopeptides bearing the Tn antigen (α-O-GalNAc-Ser/Thr) in complex with an anti MUC-1 antibody are reported at atomic resolution. For the α-O-GalNAc-Ser derivative, the glycosidic linkage adopts a high-energy conformation, barely populated in the free state. This unusual structure (also observed in an α-S-GalNAc-Cys mimic) is stabilized by hydrogen bonds between the peptidic fragment and the sugar. The selection of a particular peptide structure by the antibody is thus propagated to the carbohydrate through carbohydrate/peptide contacts, which force a change in the orientation of the sugar moiety. This seems to be unfeasible in the α-O-GalNAc-Thr glycopeptide owing to the more limited flexibility of the side chain imposed by the methyl group. Our data demonstrate the non-equivalence of Ser and Thr O-glycosylation points in molecular recognition processes. These features provide insight into the occurrence in nature of the APDTRP epitope for anti-MUC1 antibodies.
dc.description.sponsorshipWe thank the Ministerio de Econom a y Competitividad/FEDER (project CTQ2012-36365, CTQ2012-32065, BFU2010-19504, CTQ2013-44367-C2-2-P, UNLR13-4E-1931 and grant I.C.) and DGA (B89) for financial support. N.M.-S. and D.M. thank Universidad de La Rioja for FPI grants. We thank Katherine Stott (Department of Biochemistry, Cambridge University) for technical help with the BLI experiments. G.J.L.B. thanks financial support from the EPSRC. G.J.L.B. is a Royal Society University Research Fellow. M.S. thanks the Generalitat de Catalunya and Universitat Rovira i Virgili for financial support.
dc.languageEnglish
dc.language.isoen
dc.publisherWiley
dc.rightsAttribution 2.0 UK: England & Wales
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/
dc.subjectantibodies
dc.subjectconformation analysis
dc.subjectglycopeptides
dc.subjectmolecular recognition
dc.subjectX-ray diffraction
dc.titleDeciphering the Non-Equivalence of Serine and Threonine O-Glycosylation Points: Implications for Molecular Recognition of the Tn Antigen by an anti-MUC1 Antibody.
dc.typeArticle
dc.description.versionThis is the published version. It first appeared at http://onlinelibrary.wiley.com/doi/10.1002/anie.201502813/abstract.
prism.endingPage9834
prism.publicationDate2015
prism.publicationNameAngew Chem Int Ed Engl
prism.startingPage9830
prism.volume54
dc.rioxxterms.funderEPSRC
dc.rioxxterms.funderEU FP7
rioxxterms.versionofrecord10.1002/anie.201502813
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2015-06-26
dc.contributor.orcidLopes Bernardes, Goncalo [0000-0001-6594-8917]
dc.identifier.eissn1521-3773
rioxxterms.typeJournal Article/Review
cam.issuedOnline2015-06-26


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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales