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| | <StructureSection load='6bae' size='340' side='right'caption='[[6bae]], [[Resolution|resolution]] 2.14Å' scene=''> | | <StructureSection load='6bae' size='340' side='right'caption='[[6bae]], [[Resolution|resolution]] 2.14Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6bae]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BAE OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6BAE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6bae]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Finegoldia_magna Finegoldia magna], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus], [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BAE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BAE FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.14Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6b9z|6b9z]], [[6b9y|6b9y]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6bae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bae OCA], [http://pdbe.org/6bae PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bae RCSB], [http://www.ebi.ac.uk/pdbsum/6bae PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bae ProSAT]</span></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=6bae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bae OCA], [https://pdbe.org/6bae PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bae RCSB], [https://www.ebi.ac.uk/pdbsum/6bae PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bae ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/IGKC_HUMAN IGKC_HUMAN] Defects in IGKC are the cause of immunoglobulin kappa light chain deficiency (IGKCD) [MIM:[https://omim.org/entry/614102 614102]. IGKCD is a disease characterized by the complete absence of immunoglobulin kappa chains.<ref>PMID:3931219</ref> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/IGKC_HUMAN IGKC_HUMAN] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6bae" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6bae" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Finegoldia magna]] |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bzymek, K P]] | + | [[Category: Mus musculus]] |
| - | [[Category: King, J D]] | + | [[Category: Staphylococcus aureus]] |
| - | [[Category: Williams, J C]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Fab]] | + | [[Category: Bzymek KP]] |
| - | [[Category: Immune system]] | + | [[Category: King JD]] |
| - | [[Category: Meditope]] | + | [[Category: Williams JC]] |
| - | [[Category: Monoclonal antibody]]
| + | |
| Structural highlights
6bae is a 5 chain structure with sequence from Finegoldia magna, Homo sapiens, Mus musculus, Staphylococcus aureus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.14Å |
| Ligands: | , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
IGKC_HUMAN Defects in IGKC are the cause of immunoglobulin kappa light chain deficiency (IGKCD) [MIM:614102. IGKCD is a disease characterized by the complete absence of immunoglobulin kappa chains.[1]
Function
IGKC_HUMAN
Publication Abstract from PubMed
The high specificity and favorable pharmacological properties of monoclonal antibodies (mAbs) have prompted significant interest in re-engineering this class of molecules to add novel functionalities for enhanced therapeutic and diagnostic potential. Here, we used the high affinity, meditope-Fab interaction to template and drive the rapid, efficient, and stable site-specific formation of a disulfide bond. We demonstrate that this template-catalyzed strategy provides a consistent and reproducible means to conjugate fluorescent dyes, cytotoxins, or "click" chemistry handles to meditope-enabled mAbs (memAbs) and memFabs. More importantly, we demonstrate this covalent functionalization is achievable using natural amino acids only, opening up the opportunity to genetically encode cysteine meditope "tags" to biologics. As proof of principle, genetically encoded, cysteine meditope tags were added to the N- and/or C-termini of fluorescent proteins, nanobodies, and affibodies, each expressed in bacteria, purified to homogeneity, and efficiently conjugated to different memAbs and meFabs. We further show that multiple T-cell and Her2-targeting bispecific molecules using this strategy potently activate T-cell signaling pathways in vitro. Finally, the resulting products are highly stable as evidenced by serum stability assays (>14 d at 37 degrees C) and in vivo imaging of tumor xenographs. Collectively, the platform offers the opportunity to build and exchange an array of functional moieties, including protein biologics, among any cysteine memAb or Fab to rapidly create, test, and optimize stable, multifunctional biologics.
Template-Catalyzed, Disulfide Conjugation of Monoclonal Antibodies Using a Natural Amino Acid Tag.,King JD, Ma Y, Kuo YC, Bzymek KP, Goodstein LH, Meyer K, Moore RE, Crow D, Colcher DM, Singh G, Horne DA, Williams JC Bioconjug Chem. 2018 Jun 20;29(6):2074-2081. doi:, 10.1021/acs.bioconjchem.8b00284. Epub 2018 May 25. PMID:29763554[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Stavnezer-Nordgren J, Kekish O, Zegers BJ. Molecular defects in a human immunoglobulin kappa chain deficiency. Science. 1985 Oct 25;230(4724):458-61. PMID:3931219
- ↑ King JD, Ma Y, Kuo YC, Bzymek KP, Goodstein LH, Meyer K, Moore RE, Crow D, Colcher DM, Singh G, Horne DA, Williams JC. Template-Catalyzed, Disulfide Conjugation of Monoclonal Antibodies Using a Natural Amino Acid Tag. Bioconjug Chem. 2018 Jun 20;29(6):2074-2081. doi:, 10.1021/acs.bioconjchem.8b00284. Epub 2018 May 25. PMID:29763554 doi:http://dx.doi.org/10.1021/acs.bioconjchem.8b00284
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