7vux

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====
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==Complex structure of PD1 and 609A-Fab==
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<StructureSection load='7vux' size='340' side='right'caption='[[7vux]]' scene=''>
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<StructureSection load='7vux' size='340' side='right'caption='[[7vux]], [[Resolution|resolution]] 1.64&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7vux]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VUX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VUX FirstGlance]. <br>
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</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=7vux FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vux OCA], [https://pdbe.org/7vux PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vux RCSB], [https://www.ebi.ac.uk/pdbsum/7vux PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vux ProSAT]</span></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.64&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=THR:THREONINE'>THR</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7vux FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vux OCA], [https://pdbe.org/7vux PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vux RCSB], [https://www.ebi.ac.uk/pdbsum/7vux PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vux ProSAT]</span></td></tr>
</table>
</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/PDCD1_HUMAN PDCD1_HUMAN] Systemic lupus erythematosus;Multiple sclerosis. Systemic lupus erythematosus 2 (SLEB2) [MIM:[https://omim.org/entry/605218 605218]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.<ref>PMID:12402038</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/PDCD1_HUMAN PDCD1_HUMAN] Inhibitory cell surface receptor involved in the regulation of T-cell function during immunity and tolerance. Upon ligand binding, inhibits T-cell effector functions in an antigen-specific manner. Possible cell death inducer, in association with other factors.<ref>PMID:21276005</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Targeting PD1/PDL1 with blocking antibodies for cancer therapy has shown promising benefits in the clinic, but only approximately 20-30% of patients develop durable clinical responses to the treatment. Bispecific antibodies (BsAbs) that combine PD1/PDL1 blockade with the modulation of another immune checkpoint target may have greater potential to enhance immune checkpoint blockade therapy. In this study, we identified an anti-PD1 monoclonal antibody, 609A, whose heavy chain can pair with a variety of light chains from different antibodies while maintaining its PD1 binding/blocking activity. Taking advantage of this property and using a linear F(ab')(2) format, we successfully produced a series of tetravalent IgG-like BsAbs that simultaneously target PD1 and other immune checkpoint targets, including PDL1 and CTLA4. The BsAbs exhibited superior bioactivities in vitro and in vivo compared to their respective parental mAbs. Importantly, the BsAbs demonstrated the desired IgG-like physicochemical properties in terms of high-level expression, ease of purification to homogeneity, good stability and in vivo pharmacokinetics. In summary, we describe a novel and flexible plug-and-play platform to engineer IgG-like BsAbs with excellent development potential for clinical applications.
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A strategy for the efficient construction of anti-PD1-based bispecific antibodies with desired IgG-like properties.,Zhao J, Jiang L, Yang H, Deng L, Meng X, Ding J, Yang S, Zhao L, Xu W, Wang X, Zhu Z, Huang H MAbs. 2022 Jan-Dec;14(1):2044435. doi: 10.1080/19420862.2022.2044435. PMID:35239451<ref>PMID:35239451</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 7vux" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Antibody 3D structures|Antibody 3D structures]]
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*[[Cell death protein 3D structures|Cell death protein 3D structures]]
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Z-disk]]
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[[Category: Deng L]]
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[[Category: Ding J]]
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[[Category: Huang H]]
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[[Category: Jiang L]]
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[[Category: Meng X]]
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[[Category: Wang X]]
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[[Category: Xu W]]
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[[Category: Yang H]]
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[[Category: Yang S]]
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[[Category: Zhao J]]
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[[Category: Zhao L]]
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[[Category: Zhu Z]]

Revision as of 17:33, 29 November 2023

Complex structure of PD1 and 609A-Fab

PDB ID 7vux

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