期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 54, 期 34, 页码 9830-9834出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201502813
关键词
antibodies; conformation analysis; glycopeptides; molecular recognition; X-ray diffraction
资金
- Ministerio de Economia y Competitividad/FEDER [CTQ2012-36365, CTQ2012-32065, BFU2010-19504, CTQ2013-44367-C2-2-P, UNLR13-4E-1931]
- DGA [B89]
- Universidad de La Rioja
- EPSRC
- Generalitat de Catalunya
- Universitat Rovira i Virgili
- FP7 [BIOSTRUCTX-7687]
The structural features of MUC1-like glycopeptides bearing the Tn antigen (alpha-O-GalNAc-Ser/Thr) in complex with an anti MUC-1 antibody are reported at atomic resolution. For the alpha-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 alpha-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 alpha-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.
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