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6vqn
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Co-crystal structure of human PD-L1 complexed with Compound A== | |
| + | <StructureSection load='6vqn' size='340' side='right'caption='[[6vqn]], [[Resolution|resolution]] 2.49Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6vqn]] 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=6VQN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VQN 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]] 2.49Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=R81:N,N-(2,2-dimethyl[1,1-biphenyl]-3,3-diyl)bis(5-{[(2-hydroxyethyl)amino]methyl}pyridine-2-carboxamide)'>R81</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=6vqn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vqn OCA], [https://pdbe.org/6vqn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vqn RCSB], [https://www.ebi.ac.uk/pdbsum/6vqn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vqn ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/PD1L1_HUMAN PD1L1_HUMAN] Involved in the costimulatory signal, essential for T-cell proliferation and production of IL10 and IFNG, in an IL2-dependent and a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell proliferation and cytokine production.<ref>PMID:10581077</ref> <ref>PMID:11015443</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Programmed death-ligand 1 is a glycoprotein expressed on antigen presenting cells, hepatocytes, and tumors which upon interaction with programmed death-1, results in inhibition of antigen-specific T cell responses. Here, we report a mechanism of inhibiting programmed death-ligand 1 through small molecule-induced dimerization and internalization. This represents a mechanism of checkpoint inhibition, which differentiates from anti-programmed death-ligand 1 antibodies which function through molecular disruption of the programmed death 1 interaction. Testing of programmed death ligand 1 small molecule inhibition in a humanized mouse model of colorectal cancer results in a significant reduction in tumor size and promotes T cell proliferation. In addition, antigen-specific T and B cell responses from patients with chronic hepatitis B infection are significantly elevated upon programmed death ligand 1 small molecule inhibitor treatment. Taken together, these data identify a mechanism of small molecule-induced programmed death ligand 1 internalization with potential therapeutic implications in oncology and chronic viral infections. | ||
| - | + | Checkpoint inhibition through small molecule-induced internalization of programmed death-ligand 1.,Park JJ, Thi EP, Carpio VH, Bi Y, Cole AG, Dorsey BD, Fan K, Harasym T, Iott CL, Kadhim S, Kim JH, Lee ACH, Nguyen D, Paratala BS, Qiu R, White A, Lakshminarasimhan D, Leo C, Suto RK, Rijnbrand R, Tang S, Sofia MJ, Moore CB Nat Commun. 2021 Feb 22;12(1):1222. doi: 10.1038/s41467-021-21410-1. PMID:33619272<ref>PMID:33619272</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6vqn" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Lakshminarasimhan D]] | ||
| + | [[Category: Leo C]] | ||
| + | [[Category: Suto RK]] | ||
| + | [[Category: White A]] | ||
Current revision
Co-crystal structure of human PD-L1 complexed with Compound A
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