3eyv: Difference between revisions

<StructureSection load='3eyv' size='340' side='right'caption='[[3eyv]], [[Resolution|resolution]] 2.50&Aring;' scene=''>

<table><tr><td colspan='2'>[[3eyv]] is a 4 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=3EYV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EYV FirstGlance]. <br>

</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>

<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>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3eyv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3eyv OCA], [https://pdbe.org/3eyv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3eyv RCSB], [https://www.ebi.ac.uk/pdbsum/3eyv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3eyv ProSAT]</span></td></tr>

</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=3eyv ConSurf].

<div style="background-color:#fffaf0;">

BACKGROUND: Lewis Y (Le(y)) is a blood group-related carbohydrate that is expressed at high surface densities on the majority of epithelial carcinomas and is a promising target for antibody-based immunotherapy. A humanized Le(y)-specific antibody (hu3S193) has shown encouraging safety, pharmacokinetic and tumor-targeting properties in recently completed Phase I clinical trials. METHODOLOGY/PRINCIPAL FINDINGS: We report the three-dimensional structures for both the free (unliganded) and bound (Le(y) tetrasaccharide) hu3S193 Fab from the same crystal grown in the presence of divalent zinc ions. There is no evidence of significant conformational changes occurring in either the Le(y) carbohydrate antigen or the hu3S193 binding site, which suggests a rigid fit binding mechanism. In the crystal, the hu3S193 Fab molecules are coordinated at their protein-protein interface by two zinc ions and in solution aggregation of Fab can be initiated by zinc, but not magnesium ions. Dynamic light scattering revealed that zinc ions could initiate a sharp transition from hu3S193 Fab monomers to large multimeric aggregates in solution. CONCLUSIONS/SIGNIFICANCE: Zinc ions can mediate interactions between hu3S193 Fab in crystals and in solution. Whether metallic ion mediated aggregation of antibody occurs in vivo is not known, but the present results suggest that similar clustering mechanisms could occur when hu3S193 binds to Le(y) on cells, particularly given the high surface densities of antigen on the target tumor cells.

A possible role for metallic ions in the carbohydrate cluster recognition displayed by a lewis y specific antibody.,Farrugia W, Scott AM, Ramsland PA PLoS One. 2009 Nov 10;4(11):e7777. PMID:19901987<ref>PMID:19901987</ref>

==See Also==

*[[Antibody 3D structures|Antibody 3D structures]]

*[[3D structures of non-human antibody|3D structures of non-human antibody]]

[[Category: Large Structures]]

[[Category: Mus musculus]]

[[Category: Farrugia W]]

[[Category: Ramsland PA]]

[[Category: Scott AM]]