1s3k

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(New page: 200px<br /> <applet load="1s3k" size="450" color="white" frame="true" align="right" spinBox="true" caption="1s3k, resolution 1.90&Aring;" /> '''Crystal Structure o...)
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[[Image:1s3k.gif|left|200px]]<br />
 
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<applet load="1s3k" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1s3k, resolution 1.90&Aring;" />
 
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'''Crystal Structure of a Humanized Fab (hu3S193) in Complex with the Lewis Y Tetrasaccharide'''<br />
 
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==Overview==
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==Crystal Structure of a Humanized Fab (hu3S193) in Complex with the Lewis Y Tetrasaccharide==
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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--&gt;2)Gal(beta 1--&gt;4)[Fuc(alpha 1--&gt;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--&gt;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.
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<StructureSection load='1s3k' size='340' side='right'caption='[[1s3k]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1s3k]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S3K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1S3K FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene>, <scene name='pdbligand=PRD_900124:Lewis+Y+antigen,+alpha+anomer'>PRD_900124</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1s3k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s3k OCA], [https://pdbe.org/1s3k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1s3k RCSB], [https://www.ebi.ac.uk/pdbsum/1s3k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1s3k ProSAT]</span></td></tr>
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</table>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/s3/1s3k_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1s3k ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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--&gt;2)Gal(beta 1--&gt;4)[Fuc(alpha 1--&gt;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--&gt;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.
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==About this Structure==
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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<ref>PMID:15223322</ref>
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1S3K is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus_and_homo_sapiens Mus musculus and homo sapiens] with GOL as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1S3K OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15223322 15223322]
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</div>
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[[Category: Mus musculus and homo sapiens]]
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<div class="pdbe-citations 1s3k" style="background-color:#fffaf0;"></div>
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[[Category: Protein complex]]
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[[Category: Bradford, T.M.]]
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[[Category: Farrugia, W.]]
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[[Category: Hogarth, P.M.]]
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[[Category: Ramsland, P.A.]]
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[[Category: Scott, A.M.]]
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[[Category: GOL]]
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[[Category: antigen binding fragment]]
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[[Category: beta barrel]]
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[[Category: humanized antibody]]
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[[Category: immunoglobulin fold]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 18 09:41:59 2007''
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==See Also==
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*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
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[[Category: Mus musculus]]
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[[Category: Bradford TM]]
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[[Category: Farrugia W]]
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[[Category: Hogarth PM]]
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[[Category: Ramsland PA]]
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[[Category: Scott AM]]

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

PDB ID 1s3k

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