1s3k: Difference between revisions
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==Overview== | ==Overview== | ||
Antibodies targeting human epithelial carcinomas bearing Lewis Y (Le(y)) | 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 Structure== | ==About this Structure== | ||
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[[Category: Mus musculus and homo sapiens]] | [[Category: Mus musculus and homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Bradford, T | [[Category: Bradford, T M.]] | ||
[[Category: Farrugia, W.]] | [[Category: Farrugia, W.]] | ||
[[Category: Hogarth, P | [[Category: Hogarth, P M.]] | ||
[[Category: Ramsland, P | [[Category: Ramsland, P A.]] | ||
[[Category: Scott, A | [[Category: Scott, A M.]] | ||
[[Category: GOL]] | [[Category: GOL]] | ||
[[Category: antigen binding fragment]] | [[Category: antigen binding fragment]] | ||
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[[Category: immunoglobulin fold]] | [[Category: immunoglobulin fold]] | ||
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Revision as of 15:57, 21 February 2008
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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 with as ligand. 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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