title: Deciphering the Non-Equivalence of Serine and Threonine O-Glycosylation Points: Implications for Molecular Recognition of the Tn Antigen by an anti-MUC1 Antibody.
abstract: The 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.
authors.affiliation: Departamento de Química, Universidad de La Rioja, Centro de Investigación en Síntesis Química, 26006 Logroño (Spain).|Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW (UK).
authors.forename: Nuria
authors.initials: N
authors.lastname: Martínez-Sáez
authors.affiliation: Institute of Biocomputation and Physics of Complex Systems (BIFI), University of Zaragoza, BIFI-IQFR (CSIC) Joint Unit, Edificio I+D, 50018 Zaragoza (Spain).|Fundación ARAID, Edificio Pignatelli 36, Zaragoza (Spain).
authors.forename: Jorge
authors.initials: J
authors.lastname: Castro-López
authors.affiliation: Institute of Biocomputation and Physics of Complex Systems (BIFI), University of Zaragoza, BIFI-IQFR (CSIC) Joint Unit, Edificio I+D, 50018 Zaragoza (Spain).|Fundación ARAID, Edificio Pignatelli 36, Zaragoza (Spain).
authors.forename: Jessika
authors.initials: J
authors.lastname: Valero-González
authors.affiliation: Departamento de Química, Universidad de La Rioja, Centro de Investigación en Síntesis Química, 26006 Logroño (Spain).
authors.forename: David
authors.initials: D
authors.lastname: Madariaga
authors.affiliation: Departamento de Química, Universidad de La Rioja, Centro de Investigación en Síntesis Química, 26006 Logroño (Spain).
authors.forename: Ismael
authors.initials: I
authors.lastname: Compañón
authors.affiliation: Departamento de Química, Universidad de La Rioja, Centro de Investigación en Síntesis Química, 26006 Logroño (Spain).|Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW (UK).
authors.forename: Víctor J
authors.initials: VJ
authors.lastname: Somovilla
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW (UK).|Departament de Química Analítica i Química Orgànica, Universitat Rovira i Virgili, C/Marcellí Domingo s/n, 43007 Tarragona (Spain).
authors.forename: Míriam
authors.initials: M
authors.lastname: Salvadó
authors.affiliation: Instituto de Química Orgánica General, IQOG-CSIC, Juan de la Cierva 3, 28006 Madrid (Spain).
authors.forename: Juan L
authors.initials: JL
authors.lastname: Asensio
authors.affiliation: Structural Biology Unit, CIC bioGUNE, Parque Tecnológico de Bizkaia Building 801 A, 48160 Derio (Spain).|IKERBASQUE, Basque Foundation for Science, 48011 Bilbao (Spain).|Department of Chemical and Physical Biology, Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu 9, 28040 Madrid (Spain).
authors.forename: Jesús
authors.initials: J
authors.lastname: Jiménez-Barbero
authors.affiliation: Departamento de Química, Universidad de La Rioja, Centro de Investigación en Síntesis Química, 26006 Logroño (Spain).
authors.forename: Alberto
authors.initials: A
authors.lastname: Avenoza
authors.affiliation: Departamento de Química, Universidad de La Rioja, Centro de Investigación en Síntesis Química, 26006 Logroño (Spain).
authors.forename: Jesús H
authors.initials: JH
authors.lastname: Busto
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW (UK).|Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa (Portugal).
authors.forename: Gonçalo J L
authors.initials: GJ
authors.lastname: Bernardes
authors.affiliation: Departamento de Química, Universidad de La Rioja, Centro de Investigación en Síntesis Química, 26006 Logroño (Spain). jesusmanuel.peregrina@unirioja.es.
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Peregrina
authors.affiliation: Institute of Biocomputation and Physics of Complex Systems (BIFI), University of Zaragoza, BIFI-IQFR (CSIC) Joint Unit, Edificio I+D, 50018 Zaragoza (Spain). rhurtado@bifi.es.|Fundación ARAID, Edificio Pignatelli 36, Zaragoza (Spain). rhurtado@bifi.es.
authors.forename: Ramón
authors.initials: R
authors.lastname: Hurtado-Guerrero
authors.affiliation: Departamento de Química, Universidad de La Rioja, Centro de Investigación en Síntesis Química, 26006 Logroño (Spain). francisco.corzana@unirioja.es.
authors.forename: Francisco
authors.initials: F
authors.lastname: Corzana
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry / Q000276:immunology*; D006031:Glycosylation; D008958:Models, Molecular; D008968:Molecular Conformation; D018396:Mucin-1 / Q000737:chemistry / Q000276:immunology*; D012694:Serine / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D013912:Threonine / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate; D018396:Mucin-1; C040286:Tn antigen; D013912:Threonine; D012694:Serine
keywords: X-ray diffraction; antibodies; conformation analysis; glycopeptides; molecular recognition