5A2K

Crystal structure of scFv-SM3 in complex with APD-TGalNAc-RP

Summary for 5A2K

• Entry DOI: 10.2210/pdb5a2k/pdb
• Related: 5A2I 5A2J 5A2L
• Descriptor: IG LAMBDA-1 CHAIN V REGION S43, ANTIGEN TN, THR IS COVALENTLY BOUND TO GALNAC, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: immune system, glycopeptides, antibodies, molecular recognition, conformation analysis, fusion protein
• Biological source: MUS MUSCULUS (HOUSE MOUSE); More
• Total number of polymer chains: 2
• Total formula weight: 26992.66

Authors

Martinez-Saez, N.,Castro-Lopez, J.,Valero-Gonzalez, J.,Madariaga, D.,Companon, I.,Somovilla, V.J.,Salvado, M.,Asensio, J.L.,Jimenez-Barbero, J.,Avenoza, A.,Busto, J.H.,Bernardes, G.J.L.,Peregrina, J.M.,Hurtado-Guerrero, R.,Corzana, F. (deposition date: 2015-05-20, release date: 2015-06-03, Last modification date: 2024-11-13)

Primary citation

Martinez-Saez, N.,Castro-Lopez, J.,Valero-Gonzalez, J.,Madariaga, D.,Companon, I.,Somovilla, V.J.,Salvado, M.,Asensio, J.L.,Jimenez-Barbero, J.,Avenoza, A.,Busto, J.H.,Bernardes, G.J.L.,Peregrina, J.M.,Hurtado-Guerrero, R.,Corzana, F.
Deciphering the Non-Equivalence of Serine and Threonine O-Glycosylation Points: Implications for Molecular Recognition of the Tn Antigen by an Anti-Muc1 Antibody.
Angew.Chem.Int.Ed.Engl., 54:9830-, 2015

PubMed 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.

PubMed: 26118689
DOI: 10.1002/ANIE.201502813

Experimental method

X-RAY DIFFRACTION (1.7 Å)