6ghg: Difference between revisions
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The | ==Variable heavy - variable light domain and Fab-arm CrossMabs with charged residue exchanges== | ||
<StructureSection load='6ghg' size='340' side='right' caption='[[6ghg]], [[Resolution|resolution]] 1.88Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6ghg]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GHG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GHG FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ghg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ghg OCA], [http://pdbe.org/6ghg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ghg RCSB], [http://www.ebi.ac.uk/pdbsum/6ghg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ghg ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Technologies for the production of bispecific antibodies need to overcome two major challenges. The first one is correct heavy chain assembly, which was solved by knobs-into-holes technology or charge interactions in the CH3 domains. The second challenge is correct light chain assembly. This can be solved by engineering the Fab-arm interfaces or applying the immunoglobulin domain crossover approach. There are three different crossovers possible, namely Fab-arm, constant domain and variable domain crossovers. The CrossMabCH1-CL exchange does not lead to the formation of unexpected side products, whereas the CrossMabFab and the CrossMabVH-VL formats result in the formation of typical side products. Thus, CrossMabCH1-CL was initially favored for therapeutic antibody development. Here, we report a novel improved CrossMab design principle making use of site-specific positional exchanges of charged amino acid pairs in the constant domain of these CrossMabs to enable the correct light chain assembly in the CrossMabVH-VL and improvements for the CrossMabFab design. | |||
Variable heavy-variable light domain and Fab-arm CrossMabs with charged residue exchanges to enforce correct light chain assembly.,Regula JT, Imhof-Jung S, Molhoj M, Benz J, Ehler A, Bujotzek A, Schaefer W, Klein C Protein Eng Des Sel. 2018 Aug 28. pii: 5085589. doi: 10.1093/protein/gzy021. PMID:30169707<ref>PMID:30169707</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6ghg" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Benz, J]] | |||
[[Category: Bujotzek, A]] | |||
[[Category: Ehler, A]] | [[Category: Ehler, A]] | ||
[[Category: | [[Category: Imhof-Jung, S]] | ||
[[Category: Klein, C]] | |||
[[Category: Molhoj, M]] | [[Category: Molhoj, M]] | ||
[[Category: Regula, J]] | [[Category: Regula, J]] | ||
[[Category: | [[Category: Schaefer, W]] | ||
[[Category: | [[Category: Ang2]] | ||
[[Category: | [[Category: Antibody]] | ||
[[Category: | [[Category: Charge variant]] | ||
[[Category: Crossmab]] | |||
[[Category: Dp47]] | |||
[[Category: Fab fragment]] | |||
[[Category: Immune system]] | |||
[[Category: Vegf]] | |||
