View source for 5j89


==Structure of human Programmed cell death 1 ligand 1 (PD-L1) with low molecular mass inhibitor==
<StructureSection load='5j89' size='340' side='right'caption='[[5j89]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5j89]] is a 4 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=5J89 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5J89 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6GX:N-{2-[({2-METHOXY-6-[(2-METHYL[1,1-BIPHENYL]-3-YL)METHOXY]PYRIDIN-3-YL}METHYL)AMINO]ETHYL}ACETAMIDE'>6GX</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=5j89 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j89 OCA], [https://pdbe.org/5j89 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5j89 RCSB], [https://www.ebi.ac.uk/pdbsum/5j89 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5j89 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 ==
Targeting the PD-1/PD-L1 immunologic checkpoint with monoclonal antibodies has provided unprecedented results in cancer treatment in the recent years. Development of chemical inhibitors for this pathway lags the antibody development because of insufficient structural information. The first nonpeptidic chemical inhibitors that target the PD-1/PD-L1 interaction have only been recently disclosed by Bristol-Myers Squibb. Here, we show that these small-molecule compounds bind directly to PD-L1 and that they potently block PD-1 binding. Structural studies reveal a dimeric protein complex with a single small molecule which stabilizes the dimer thus occluding the PD-1 interaction surface of PD-L1s. The small-molecule interaction "hot spots" on PD-L1 surfaces suggest approaches for the PD-1/PD-L1 antagonist drug discovery.

Structural basis for small molecule targeting of the programmed death ligand 1 (PD-L1).,Zak KM, Grudnik P, Guzik K, Zieba BJ, Musielak B, Domling A, Dubin G, Holak TA Oncotarget. 2016 Apr 13. doi: 10.18632/oncotarget.8730. PMID:27083005<ref>PMID:27083005</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5j89" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Doemling P]]
[[Category: Dubin G]]
[[Category: Grudnik P]]
[[Category: Guzik K]]
[[Category: Holak TA]]
[[Category: Musielak B]]
[[Category: Zak KM]]
[[Category: Zieba BJ]]