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Deciphering the non-equivalence of serine and threonine o-glycosylation points: implications for molecular recognition of the Tn antigen by an anti-MUC1 antibody

DOI: 10.1002/anie.201502813 DOI Help
PMID: 26118689 PMID Help

Authors: Nuria Martínez-Sáez (Universidad de La Rioja) , Jorge Castro-López (University of Zaragoza) , Jessika Valero-González (University of Zaragoza) , David Madariaga (Universidad de La Rioja) , Ismael Compañón (Universidad de La Rioja) , Víctor J. Somovilla (Universidad de La Rioja) , Míriam Salvadó (University of Cambridge) , Juan L. Asensio (Instituto de Química Orgánica General) , Jesús Jiménez-Barbero (Universidad de La Rioja) , Alberto Avenoza (Universidad de La Rioja) , Jesús H. Busto (Universidad de La Rioja) , Gonçalo J. L. Bernardes (University of Cambridge) , Jesús M. Peregrina (Universidad de La Rioja) , Ramón Hurtado-Guerrero (University of Zaragoza) , Francisco Corzana (Universidad de La Rioja)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Angewandte Chemie International Edition , VOL 54 (34) , PAGES 9830 - 9834

State: Published (Approved)
Published: August 2015
Diamond Proposal Number(s): 10121 , 8035

Open Access Open Access

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.

Journal Keywords: Antibodies; Conformation Analysis; Glycopeptides; Molecular Recognition; X-Ray Diffraction

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: I02-Macromolecular Crystallography , I04-Macromolecular Crystallography

Added On: 24/09/2015 13:15

Angew Chem Int Ed - 2015 - Mart nez‐S ez - Deciphering the Non‐Equivalence of Serine and Threonine O‐Glycosylation Points .pdf

Discipline Tags:

Non-Communicable Diseases Health & Wellbeing Cancer Biochemistry Chemistry Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)