View source for 5vsi


==CH1/Ckappa Fab mutant 15.1==
<StructureSection load='5vsi' size='340' side='right'caption='[[5vsi]], [[Resolution|resolution]] 1.51&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5vsi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VSI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VSI 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]] 1.51&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5vsi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vsi OCA], [https://pdbe.org/5vsi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vsi RCSB], [https://www.ebi.ac.uk/pdbsum/5vsi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vsi ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q6GMX6_HUMAN Q6GMX6_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The use of bispecific antibodies (BsAbs) to treat human diseases is on the rise. Increasingly complex and powerful therapeutic mechanisms made possible by BsAbs are spurring innovation of novel BsAb formats and methods for their production. The long-lived in vivo pharmacokinetics, optimal biophysical properties and potential effector functions of natural IgG monoclonal (and monospecific) antibodies has resulted in a push to generate fully IgG BsAb formats with the same quaternary structure as monoclonal IgGs. The production of fully IgG BsAbs is challenging because of the highly heterogeneous pairing of heavy chains (HCs) and light chains (LCs) when produced in mammalian cells with two IgG HCs and two LCs. A solution to the HC heterodimerization aspect of IgG BsAb production was first discovered two decades ago; however, addressing the LC mispairing issue has remained intractable until recently. Here, we use computational and rational engineering to develop novel designs to the HC/LC pairing issue, and particularly for kappa LCs. Crystal structures of these designs highlight the interactions that provide HC/LC specificity. We produce and characterize multiple fully IgG BsAbs using these novel designs. We demonstrate the importance of specificity engineering in both the variable and constant domains to achieve robust HC/LC specificity within all the BsAbs. These solutions facilitate the production of fully IgG BsAbs for clinical use.

Computational design of a specific heavy chain/kappa light chain interface for expressing fully IgG bispecific antibodies.,Froning KJ, Leaver-Fay A, Wu X, Phan S, Gao L, Huang F, Pustilnik A, Bacica M, Houlihan K, Chai Q, Fitchett JR, Hendle J, Kuhlman B, Demarest SJ Protein Sci. 2017 Jul 20. doi: 10.1002/pro.3240. PMID:28726352<ref>PMID:28726352</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5vsi" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Hendle J]]