View source for 8guz


==Crystal structure of anti-FIXa IgG fab with FAST-Ig mutations==
<StructureSection load='8guz' size='340' side='right'caption='[[8guz]], [[Resolution|resolution]] 1.79&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8guz]] is a 4 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=8GUZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GUZ 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]] 1.79&#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></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=8guz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8guz OCA], [https://pdbe.org/8guz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8guz RCSB], [https://www.ebi.ac.uk/pdbsum/8guz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8guz ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Efficient production of bispecific antibodies (BsAbs) in single mammalian cells is essential for basic research and industrial manufacturing. However, preventing unwanted pairing of heavy chains (HCs) and light chains (LCs) is a challenging task. To address this, we created an engineering technology for preferential cognate HC/LC and HC/HC paring called FAST-Ig (Four-chain Assembly by electrostatic Steering Technology - Immunoglobulin), and applied it to NXT007, a BsAb for the treatment of hemophilia A. We introduced charged amino-acid substitutions at the HC/LC interface to facilitate the proper assembly for manufacturing a standard IgG-type BsAb. We generated CH1/CL interface-engineered antibody variants that achieved &gt; 95% correct HC/LC pairing efficiency with favorable pharmacological properties and developability. Among these, we selected a design (C3) that allowed us to separate the mis-paired species with an unintended pharmacological profile using ion-exchange chromatography. Crystal structure analysis demonstrated that the C3 design did not affect the overall structure of both Fabs. To determine the final design for HCs-heterodimerization, we compared the stability of charge-based and knobs into hole-based Fc formats in acidic conditions and selected the more stable charge-based format. FAST-Ig was also applicable to stable CHO cell lines for industrial production and demonstrated robust chain pairing with different subclasses of parent BsAbs. Thus, it can be applied to a wide variety of BsAbs both preclinically and clinically.

Efficient production of bispecific antibody by FAST-Ig(TM) and its application to NXT007 for the treatment of hemophilia A.,Koga H, Yamano T, Betancur J, Nagatomo S, Ikeda Y, Yamaguchi K, Nabuchi Y, Sato K, Teranishi-Ikawa Y, Sato M, Hirayama H, Hayasaka A, Torizawa T, Haraya K, Sampei Z, Shiraiwa H, Kitazawa T, Igawa T, Kuramochi T MAbs. 2023 Jan-Dec;15(1):2222441. doi: 10.1080/19420862.2023.2222441. PMID:37339067<ref>PMID:37339067</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8guz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Fukami TA]]
[[Category: Koga H]]
[[Category: Sampei Z]]
[[Category: Shiraiwa H]]
[[Category: Torizawa T]]
[[Category: Yamano T]]