6pyd: Difference between revisions
New page: '''Unreleased structure''' The entry 6pyd is ON HOLD Authors: Description: Category: Unreleased Structures |
No edit summary |
||
(4 intermediate revisions by the same user not shown) | |||
Line 1: | Line 1: | ||
==Structure of 3E9 antibody Fab bound to marinobufagenin== | |||
<StructureSection load='6pyd' size='340' side='right'caption='[[6pyd]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6pyd]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PYD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PYD 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]] 2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P4S:(3beta,5beta,14alpha,15beta)-3,5-dihydroxy-14,15-epoxybufa-20,22-dienolide'>P4S</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=6pyd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pyd OCA], [https://pdbe.org/6pyd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pyd RCSB], [https://www.ebi.ac.uk/pdbsum/6pyd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pyd ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:31879340</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6pyd" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | |||
*[[Sandbox 20009|Sandbox 20009]] | |||
*[[3D structures of non-human antibody|3D structures of non-human antibody]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Franklin MC]] | |||
[[Category: Macdonald LE]] | |||
[[Category: McWhirter J]] | |||
[[Category: Murphy AJ]] |
Latest revision as of 10:38, 11 October 2023
Structure of 3E9 antibody Fab bound to marinobufageninStructure of 3E9 antibody Fab bound to marinobufagenin
Structural highlights
Publication Abstract from PubMedWe 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
|