1S3K

Crystal Structure of a Humanized Fab (hu3S193) in Complex with the Lewis Y Tetrasaccharide

Summary for 1S3K

• Entry DOI: 10.2210/pdb1s3k/pdb
• Related PRD ID: PRD_900124
• Descriptor: HU3S193 Fab fragment, light chain, HU3S193 Fab fragment, heavy chain, alpha-L-fucopyranose-(1-2)-beta-D-galactopyranose-(1-4)-[alpha-L-fucopyranose-(1-3)]2-acetamido-2-deoxy-alpha-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: immunoglobulin fold, beta barrel, humanized antibody, antigen binding fragment, immune system
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 2
• Total formula weight: 48631.07

Authors

Ramsland, P.A.,Farrugia, W.,Bradford, T.M.,Hogarth, P.M.,Scott, A.M. (deposition date: 2004-01-13, release date: 2004-07-13, Last modification date: 2024-10-30)

Primary citation

Ramsland, P.A.,Farrugia, W.,Bradford, T.M.,Hogarth, P.M.,Scott, A.M.
Structural convergence of antibody binding of carbohydrate determinants in lewis y tumor antigens
J.Mol.Biol., 340:809-818, 2004

PubMed Abstract: Antibodies targeting human epithelial carcinomas bearing Lewis Y (Le(y)) carbohydrate antigens provide a striking illustration of convergent immune recognition. We report a 1.9A resolution crystal structure of the Fab of a humanized antibody (hu3S193) in complex with the Le(y) tetrasaccharide, Fuc(alpha 1-->2)Gal(beta 1-->4)[Fuc(alpha 1-->3)]GlcNAc. Comparisons of the hu3S193 and BR96 antibodies bound to Le(y) tumor antigens revealed extremely similar mechanisms for recognition of the carbohydrate epitopes. Solvent plays a critical role in hu3S193 antibody binding to the Le(y) carbohydrate epitope. Specificity for Le(y) is maintained because a conserved pocket accepts an N-acetyl group of the core Gal(beta 1-->4)GlcNAc disaccharide. Closely related blood-group determinants (Le(a) and Le(b)) cannot enter the specificity pocket, making the Le(y) antibodies promising candidates for immunotherapy of epithelial cancer.

PubMed: 15223322
DOI: 10.1016/j.jmb.2004.05.037

Experimental method

X-RAY DIFFRACTION (1.9 Å)