5vsi | pdb_00005vsi

CH1/Ckappa Fab mutant 15.1

spinqualitylabelsall models 5vsi, resolution 1.51Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5vsi is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EDO, SO4 NonStd Res: PCA Related: 5vr9, 5vsh Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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