6XUN
Ab 5b1 bound to CA19-9
Summary for 6XUN
| Entry DOI | 10.2210/pdb6xun/pdb |
| Descriptor | Heavy chain, Light chain, N-acetyl-alpha-neuraminic acid-(2-3)-beta-D-galactopyranose-(1-3)-[alpha-L-fucopyranose-(1-4)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total) |
| Functional Keywords | pancreatic cancer, ca19-9 binder, diagnosis, immunotherapy reagent, immunotheraeutic agent, antitumor protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 6 |
| Total formula weight | 147870.54 |
| Authors | Diskin, R.,Borenstein-Katz, A. (deposition date: 2020-01-20, release date: 2021-02-03, Last modification date: 2024-11-13) |
| Primary citation | Borenstein-Katz, A.,Warszawski, S.,Amon, R.,Eilon, M.,Cohen-Dvashi, H.,Leviatan Ben-Arye, S.,Tasnima, N.,Yu, H.,Chen, X.,Padler-Karavani, V.,Fleishman, S.J.,Diskin, R. Biomolecular Recognition of the Glycan Neoantigen CA19-9 by Distinct Antibodies. J.Mol.Biol., 433:167099-167099, 2021 Cited by PubMed Abstract: Glycans decorate the cell surface, secreted glycoproteins and glycolipids, and altered glycans are often found in cancers. Despite their high diagnostic and therapeutic potential, however, glycans are polar and flexible molecules that are quite challenging for the development and design of high-affinity binding antibodies. To understand the mechanisms by which glycan neoantigens are specifically recognized by antibodies, we analyze the biomolecular recognition of the tumor-associated carbohydrate antigen CA19-9 by two distinct antibodies using X-ray crystallography. Despite the potential plasticity of glycans and the very different antigen-binding surfaces presented by the antibodies, both structures reveal an essentially identical extended CA19-9 conformer, suggesting that this conformer's stability selects the antibodies. Starting from the bound structure of one of the antibodies, we use the AbLIFT computational algorithm to design a variant with seven core mutations in the variable domain's light-heavy chain interface that exhibits tenfold improved affinity for CA19-9. The results reveal strategies used by antibodies to specifically recognize glycan antigens and show how automated antibody-optimization methods may be used to enhance the clinical potential of existing antibodies. PubMed: 34119488DOI: 10.1016/j.jmb.2021.167099 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.41 Å) |
Structure validation
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