5n7b | pdb_00005n7b

Understanding the singular conformational landscape of the Tn antigens: Sulfur-for- oxygen substitution in the glycosidic linkage provides new insights into molecular recognition by an antibody

spinqualitylabelsall models 5n7b, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5n7b is a 2 chain structure with sequence from Mus musculus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.7Å Ligands: A2G, CG6, EDO, NH2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function HVM32_MOUSE LV1E_MOUSE Publication Abstract from PubMed GalNAc-glycopeptides derived from mucin MUC1 are an important class of tumor-associated antigens. alpha- O-glycosylation forces the peptide to adopt an extended conformation in solution, which is far from the structure observed in complexes with a model anti-MUC1 antibody. Herein, we propose a new strategy for designing potent antigen mimics based on modulating peptide/carbohydrate interactions by means of O --> S/Se replacement at the glycosidic linkage. These minimal chemical modifications bring about two key structural changes to the glycopeptide. They increase the carbohydrate-peptide distance and change the orientation and dynamics of the glycosidic linkage. As a result, the peptide acquires a preorganized and optimal structure suited for antibody binding. Accordingly, these new glycopeptides display improved binding toward a representative anti-MUC1 antibody relative to the native antigens. To prove the potential of these glycopeptides as tumor-associated MUC1 antigen mimics, the derivative bearing the S-glycosidic linkage was conjugated to gold nanoparticles and tested as an immunogenic formulation in mice without any adjuvant, which resulted in a significant humoral immune response. Importantly, the mice antisera recognize cancer cells in biopsies of breast cancer patients with high selectivity. This finding demonstrates that the antibodies elicited against the mimetic antigen indeed recognize the naturally occurring antigen in its physiological context. Clinically, the exploitation of tumor-associated antigen mimics may contribute to the development of cancer vaccines and to the improvement of cancer diagnosis based on anti-MUC1 antibodies. The methodology presented here is of general interest for applications because it may be extended to modulate the affinity of biologically relevant glycopeptides toward their receptors. Structure-Based Design of Potent Tumor-Associated Antigens: Modulation of Peptide Presentation by Single-Atom O/S or O/Se Substitutions at the Glycosidic Linkage.,Companon I, Guerreiro A, Mangini V, Castro-Lopez J, Escudero-Casao M, Avenoza A, Busto JH, Castillon S, Jimenez-Barbero J, Asensio JL, Jimenez-Oses G, Boutureira O, Peregrina JM, Hurtado-Guerrero R, Fiammengo R, Bernardes GJL, Corzana F J Am Chem Soc. 2019 Feb 20. doi: 10.1021/jacs.8b13503. PMID:30726084 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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