1s3k
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, resolution 1.90Å | |||||||
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Ligands: | , , , | ||||||
Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
Coordinates: | save as pdb, mmCIF, xml |
Crystal Structure of a Humanized Fab (hu3S193) in Complex with the Lewis Y Tetrasaccharide
OverviewOverview
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.
About this StructureAbout this Structure
1S3K is a Protein complex structure of sequences from Mus musculus and homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structural convergence of antibody binding of carbohydrate determinants in Lewis Y tumor antigens., Ramsland PA, Farrugia W, Bradford TM, Mark Hogarth P, Scott AM, J Mol Biol. 2004 Jul 16;340(4):809-18. PMID:15223322
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