View source for 4ma3


==Crystal structure of anti-hinge rabbit antibody C2095==
<StructureSection load='4ma3' size='340' side='right'caption='[[4ma3]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ma3]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MA3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MA3 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4ma3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ma3 OCA], [https://pdbe.org/4ma3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ma3 RCSB], [https://www.ebi.ac.uk/pdbsum/4ma3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ma3 ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
The 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<ref>PMID:24638881</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Oryctolagus cuniculus]]
[[Category: Gilliland GL]]
[[Category: Malia T]]
[[Category: Teplyakov A]]