6uga | pdb_00006uga

ch28/11 Fab (monoclinic form)

spinqualitylabelsall models 6uga, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6uga is a 4 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 03S Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Cancer remains a leading cause of morbidity and mortality worldwide, requiring ongoing development of targeted therapeutics such as monoclonal antibodies. Carbohydrates on embryonic cells are often highly expressed in cancer and are therefore attractive targets for antibodies. Stage-specific embryonic antigen-4 (SSEA-4) is one such glycolipid target expressed in many cancers, including breast and ovarian carcinomas. Here, we defined the structural basis for recognition of SSEA-4 by a novel monospecific chimeric antibody (ch28/11). Five X-ray structures of ch28/11 Fab complexes with the SSEA-4 glycan headgroup, determined at 1.5-2.7 A resolutions, displayed highly similar 3D structures indicating a stable binding mode. The structures also revealed that by adopting a horseshoe-shaped conformation in a deep groove, the glycan headgroup likely sits flat against the membrane to allow the antibody to interact with SSEA-4 on cancer cells. Moreover, we found that the terminal sialic acid of SSEA-4 plays a dominant role in dictating the exquisite specificity of the ch28/11 antibody. This observation was further supported by molecular dynamics simulations of the ch28/11-glycan complex, which show SSEA-4 is stabilized by its terminal sialic acid, unlike SSEA-3 which lacks this sialic acid modification. These high-resolution views of how a glycolipid interacts with an antibody may help advance a new class of cancer-targeting immunotherapy. The terminal sialic acid of stage-specific embryonic antigen-4 has a crucial role in binding to a cancer-targeting antibody.,Soliman C, Chua JX, Vankemmelbeke M, McIntosh RS, Guy AJ, Spendlove I, Durrant LG, Ramsland PA J Biol Chem. 2019 Dec 12. pii: RA119.011518. doi: 10.1074/jbc.RA119.011518. PMID:31831622 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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