7nld
From Proteopedia
(Difference between revisions)
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==Structure of human Programmed cell death 1 ligand 1 (PD-L1) with low molecular mass inhibitor== | ==Structure of human Programmed cell death 1 ligand 1 (PD-L1) with low molecular mass inhibitor== | ||
| - | <StructureSection load='7nld' size='340' side='right'caption='[[7nld]]' scene=''> | + | <StructureSection load='7nld' size='340' side='right'caption='[[7nld]], [[Resolution|resolution]] 2.30Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NLD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NLD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7nld]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NLD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NLD FirstGlance]. <br> |
| - | </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=7nld FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nld OCA], [https://pdbe.org/7nld PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nld RCSB], [https://www.ebi.ac.uk/pdbsum/7nld PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nld ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UGZ:N-(2-((2-chloro-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-3-methoxy-[1,1-biphenyl]-4-yl)(methyl)amino)ethyl)methanesulfonamide'>UGZ</scene></td></tr> |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CD274, B7H1, PDCD1L1, PDCD1LG1, PDL1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=7nld FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nld OCA], [https://pdbe.org/7nld PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nld RCSB], [https://www.ebi.ac.uk/pdbsum/7nld PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nld ProSAT]</span></td></tr> | ||
</table> | </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 == | ||
| + | We describe a new class of potent PD-L1/PD-1 inhibitors based on a terphenyl scaffold that is derived from the rigidified biphenyl-inspired structure. Using in silico docking, we designed and then experimentally demonstrated the effectiveness of the terphenyl-based scaffolds in inhibiting PD-1/PD-L1 complex formation using various biophysical and biochemical techniques. We also present a high-resolution structure of the complex of PD-L1 with one of our most potent inhibitors to identify key PD-L1/inhibitor interactions at the molecular level. In addition, we show the efficacy of our most potent inhibitors in activating the antitumor response using primary human immune cells from healthy donors. | ||
| + | |||
| + | Terphenyl-Based Small-Molecule Inhibitors of Programmed Cell Death-1/Programmed Death-Ligand 1 Protein-Protein Interaction.,Muszak D, Surmiak E, Plewka J, Magiera-Mularz K, Kocik-Krol J, Musielak B, Sala D, Kitel R, Stec M, Weglarczyk K, Siedlar M, Domling A, Skalniak L, Holak TA J Med Chem. 2021 Jul 27. doi: 10.1021/acs.jmedchem.1c00957. PMID:34313116<ref>PMID:34313116</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7nld" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Grudnik P]] | + | [[Category: Grudnik, P]] |
| - | [[Category: Holak | + | [[Category: Holak, T A]] |
| - | [[Category: Magiera-Mularz K]] | + | [[Category: Magiera-Mularz, K]] |
| - | [[Category: Muszak D]] | + | [[Category: Muszak, D]] |
| - | [[Category: Sala D]] | + | [[Category: Sala, D]] |
| - | [[Category: Surmiak E]] | + | [[Category: Surmiak, E]] |
| + | [[Category: Cancer]] | ||
| + | [[Category: Immune system]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Pd-l1]] | ||
Revision as of 06:37, 25 August 2021
Structure of human Programmed cell death 1 ligand 1 (PD-L1) with low molecular mass inhibitor
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Categories: Human | Large Structures | Grudnik, P | Holak, T A | Magiera-Mularz, K | Muszak, D | Sala, D | Surmiak, E | Cancer | Immune system | Inhibitor | Pd-l1
