4o51: Difference between revisions
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==Crystal structure of the QAA variant of anti-hinge rabbit antibody 2095-2 in complex with IDES hinge peptide== | ==Crystal structure of the QAA variant of anti-hinge rabbit antibody 2095-2 in complex with IDES hinge peptide== | ||
<StructureSection load='4o51' size='340' side='right' caption='[[4o51]], [[Resolution|resolution]] 2.20Å' scene=''> | <StructureSection load='4o51' size='340' side='right' caption='[[4o51]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
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</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr> | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ma3|4ma3]], [[4o4y|4o4y]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ma3|4ma3]], [[4o4y|4o4y]]</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4o51 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o51 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4o51 RCSB], [http://www.ebi.ac.uk/pdbsum/4o51 PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4o51 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o51 OCA], [http://pdbe.org/4o51 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4o51 RCSB], [http://www.ebi.ac.uk/pdbsum/4o51 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4o51 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4o51" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 23:56, 11 August 2016
Crystal structure of the QAA variant of anti-hinge rabbit antibody 2095-2 in complex with IDES hinge peptideCrystal structure of the QAA variant of anti-hinge rabbit antibody 2095-2 in complex with IDES hinge peptide
Structural highlights
Publication Abstract from PubMedThe functional role of human anti-hinge (HAH) autoantibodies in normal health and disease remains elusive, but recent evidence supports their role in the host response to IgG cleavage by proteases that are prevalent in certain disorders. Characterization and potential exploitation of these HAH antibodies has been hindered by the absence of monoclonal reagents. 2095-2 is a rabbit monoclonal antibody targeting the IdeS-cleaved hinge of human IgG1. We have determined the crystal structure of the Fab of 2095-2 and its complex with a hinge analog peptide. The antibody is selective for the C-terminally cleaved hinge ending in G236 and this interaction involves an uncommon disulfide in VL CDR3. We probed the importance of the disulfide in VL CDR3 through engineering variants. We identified one variant, QAA, which does not require the disulfide for biological activity or peptide binding. The structure of this variant offers a starting point for further engineering of 2095-2 with the same specificity, but lacking the potential manufacturing liability of an additional disulfide. (c) Proteins 2014;. (c) 2014 Wiley Periodicals, Inc. Structure and specificity of an antibody targeting a proteolytically-cleaved IgG hinge.,Malia TJ, Teplyakov A, Brezski RJ, Luo J, Kinder M, Sweet RW, Almagro JC, Jordan RE, Gilliland GL Proteins. 2014 Mar 17. doi: 10.1002/prot.24545. PMID:24638881[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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