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| | ==PD-L1 IgV domain complex with macro-cyclic peptide== | | ==PD-L1 IgV domain complex with macro-cyclic peptide== |
| - | <StructureSection load='6nnv' size='340' side='right' caption='[[6nnv]], [[Resolution|resolution]] 1.92Å' scene=''> | + | <StructureSection load='6nnv' size='340' side='right'caption='[[6nnv]], [[Resolution|resolution]] 1.92Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6nnv]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NNV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NNV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6nnv]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NNV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NNV FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=9KK:'>9KK</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=MEA:N-METHYLPHENYLALANINE'>MEA</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=SAR:SARCOSINE'>SAR</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.92Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CD274, B7H1, PDCD1L1, PDCD1LG1, PDL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9KK:N-methyl+norleucine'>9KK</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=MEA:N-METHYLPHENYLALANINE'>MEA</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=SAR:SARCOSINE'>SAR</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6nnv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nnv OCA], [http://pdbe.org/6nnv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nnv RCSB], [http://www.ebi.ac.uk/pdbsum/6nnv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nnv ProSAT]</span></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=6nnv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nnv OCA], [https://pdbe.org/6nnv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nnv RCSB], [https://www.ebi.ac.uk/pdbsum/6nnv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nnv ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Perry, E]] | + | [[Category: Large Structures]] |
| - | [[Category: Zhao, B]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Cancer drug discovery]] | + | [[Category: Perry E]] |
| - | [[Category: Fragment-based screening]] | + | [[Category: Zhao B]] |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Immunotherapy]]
| + | |
| - | [[Category: Pd-l1 inhibitor]]
| + | |
| - | [[Category: Structure-based design]]
| + | |
| Structural highlights
6nnv is a 8 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.92Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
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.[1] [2]
Publication Abstract from PubMed
The PD-1 immune checkpoint pathway is a highly validated target for cancer immunotherapy. Despite the potential advantages of small molecule inhibitors over antibodies, the discovery of small molecule checkpoint inhibitors has lagged behind. To discover small molecule inhibitors of the PD-1 pathway, we have utilized a fragment-based approach. Small molecules were identified that bind to PD-L1 and crystal structures of these compounds bound to PD-L1 were obtained.
Fragment-based screening of programmed death ligand 1 (PD-L1).,Perry E, Mills JJ, Zhao B, Wang F, Sun Q, Christov PP, Tarr JC, Rietz TA, Olejniczak ET, Lee T, Fesik S Bioorg Med Chem Lett. 2019 Mar 15;29(6):786-790. doi: 10.1016/j.bmcl.2019.01.028., Epub 2019 Jan 24. PMID:30728114[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dong H, Zhu G, Tamada K, Chen L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999 Dec;5(12):1365-9. PMID:10581077 doi:10.1038/70932
- ↑ Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, Horton HF, Fouser L, Carter L, Ling V, Bowman MR, Carreno BM, Collins M, Wood CR, Honjo T. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000 Oct 2;192(7):1027-34. PMID:11015443
- ↑ Perry E, Mills JJ, Zhao B, Wang F, Sun Q, Christov PP, Tarr JC, Rietz TA, Olejniczak ET, Lee T, Fesik S. Fragment-based screening of programmed death ligand 1 (PD-L1). Bioorg Med Chem Lett. 2019 Mar 15;29(6):786-790. doi: 10.1016/j.bmcl.2019.01.028., Epub 2019 Jan 24. PMID:30728114 doi:http://dx.doi.org/10.1016/j.bmcl.2019.01.028
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