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7nld

From Proteopedia

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Current revision

Structure of human Programmed cell death 1 ligand 1 (PD-L1) with low molecular mass inhibitor

Structural highlights

7nld is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.3Å
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

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^[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
↑ 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. Terphenyl-Based Small-Molecule Inhibitors of Programmed Cell Death-1/Programmed Death-Ligand 1 Protein-Protein Interaction. J Med Chem. 2021 Jul 27. doi: 10.1021/acs.jmedchem.1c00957. PMID:34313116 doi:http://dx.doi.org/10.1021/acs.jmedchem.1c00957

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7nld"

@@ Line 3: / Line 3: @@
 <StructureSection load='7nld' size='340' side='right'caption='[[7nld]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<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>
+<table><tr><td colspan='2'>[[7nld]] is a 6 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=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='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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</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='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='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>
 == 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>
+[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 ==
@@ Line 23: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Grudnik, P]]
+[[Category: Grudnik P]]
-[[Category: Holak, T A]]
+[[Category: Holak TA]]
-[[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]]

7nld

From Proteopedia

Current revision

Structure of human Programmed cell death 1 ligand 1 (PD-L1) with low molecular mass inhibitor

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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