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8p1o
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Solubilizer tag effect on PD-L1/inhibitor binding properties for m-terphenyl derivatives== | |
| + | <StructureSection load='8p1o' size='340' side='right'caption='[[8p1o]], [[Resolution|resolution]] 2.17Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8p1o]] is a 2 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=8P1O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8P1O 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]] 2.17Å</td></tr> | ||
| + | <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=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=WEW:(3~{R})-1-[[4-[2-chloranyl-3-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-2-methoxy-phenyl]methyl]-~{N}-(2-hydroxyethyl)pyrrolidine-3-carboxamide'>WEW</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=8p1o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8p1o OCA], [https://pdbe.org/8p1o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8p1o RCSB], [https://www.ebi.ac.uk/pdbsum/8p1o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8p1o 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 == | ||
| + | Although heavily studied, the subject of anti-PD-L1 small-molecule inhibitors is still elusive. Here we present a systematic overview of the principles behind successful anti-PD-L1 small-molecule inhibitor design on the example of the m-terphenyl scaffold, with a particular focus on the neglected influence of the solubilizer tag on the overall affinity toward PD-L1. The inhibitor developed according to the proposed guidelines was characterized through its potency in blocking PD-1/PD-L1 complex formation in homogeneous time-resolved fluorescence and cell-based assays. The affinity is also explained based on the crystal structure of the inhibitor itself and its costructure with PD-L1 as well as a molecular modeling study. Our results structuralize the knowledge related to the strong pharmacophore feature of the m-terphenyl scaffold preferential geometry and the more complex role of the solubilizer tag in PD-L1 homodimer stabilization. | ||
| - | + | Solubilizer Tag Effect on PD-L1/Inhibitor Binding Properties for m-Terphenyl Derivatives.,Surmiak E, Zaber J, Plewka J, Wojtanowicz G, Kocik-Krol J, Kruc O, Muszak D, Rodriguez I, Musielak B, Viviano M, Castellano S, Skalniak L, Magiera-Mularz K, Holak TA, Kalinowska-Tluscik J ACS Med Chem Lett. 2023 Dec 14;15(1):36-44. doi: 10.1021/acsmedchemlett.3c00306. , eCollection 2024 Jan 11. PMID:38229762<ref>PMID:38229762</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8p1o" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Holak TA]] | ||
| + | [[Category: Kalinowska-Tluscik J]] | ||
| + | [[Category: Magiera-Mularz K]] | ||
| + | [[Category: Plewka J]] | ||
| + | [[Category: Surmiak E]] | ||
Current revision
Solubilizer tag effect on PD-L1/inhibitor binding properties for m-terphenyl derivatives
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