6pyc

Structure of kappa-on-heavy (KoH) antibody Fab bound to the cardiac hormone marinobufagenin

spinqualitylabelsall models 6pyc, resolution 3.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6pyc is a 4 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.6Å Ligands: P4S, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed We describe a Kappa-on-Heavy (KoH) mouse that produces a class of highly diverse, fully human, antibody-like agents. This mouse was made by replacing the germline variable sequences of both the Ig heavy-chain (IgH) and Ig kappa (IgK) loci with the human IgK germline variable sequences, producing antibody-like molecules with an antigen binding site made up of 2 kappa variable domains. These molecules, named KoH bodies, structurally mimic naturally existing Bence-Jones light-chain dimers in their variable domains and remain wild-type in their antibody constant domains. Unlike artificially diversified, nonimmunoglobulin alternative scaffolds (e.g., DARPins), KoH bodies consist of a configuration of normal Ig scaffolds that undergo natural diversification in B cells. Monoclonal KoH bodies have properties similar to those of conventional antibodies but exhibit an enhanced ability to bind small molecules such as the endogenous cardiotonic steroid marinobufagenin (MBG) and nicotine. A comparison of crystal structures of MBG bound to a KoH Fab versus a conventional Fab showed that the KoH body has a much deeper binding pocket, allowing MBG to be held 4 A further down into the combining site between the 2 variable domains. Kappa-on-Heavy (KoH) bodies are a distinct class of fully-human antibody-like therapeutic agents with antigen-binding properties.,Macdonald LE, Meagher KA, Franklin MC, Levenkova N, Hansen J, Badithe AT, Zhong M, Krueger P, Rafique A, Tu N, Shevchuk J, Wadhwa S, Ehrlich G, Bautista J, Grant C, Esau L, Poueymirou WT, Auerbach W, Morton L, Babb R, Chen G, Huang T, MacDonald D, Graham K, Gurer C, Voronina VA, McWhirter JR, Guo C, Yancopoulos GD, Murphy AJ Proc Natl Acad Sci U S A. 2019 Dec 26. pii: 1901734117. doi:, 10.1073/pnas.1901734117. PMID:31879340 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody 3D structures Sandbox 20009 3D structures of non-human antibody

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