6kya
From Proteopedia
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==Crystal structure of human TLR8 in complex TH1027== | ==Crystal structure of human TLR8 in complex TH1027== | ||
| - | <StructureSection load='6kya' size='340' side='right'caption='[[6kya]]' scene=''> | + | <StructureSection load='6kya' size='340' side='right'caption='[[6kya]], [[Resolution|resolution]] 2.89Å' 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=6KYA OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[6kya]] 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=6KYA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KYA FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.89Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=DY3:3-[5-methylsulfanyl-4-(3,4,5-trimethylphenyl)-1,2,4-triazol-3-yl]propan-1-ol'>DY3</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=6kya FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kya OCA], [https://pdbe.org/6kya PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kya RCSB], [https://www.ebi.ac.uk/pdbsum/6kya PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kya ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/TLR8_HUMAN TLR8_HUMAN] Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response.<ref>PMID:17932028</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Rational designs of small-molecule inhibitors targeting protein-protein interfaces have met little success. Herein, we have designed a series of triazole derivatives with a novel scaffold to specifically intervene with the interaction of TLR8 homomerization. In multiple assays, TH1027 was identified as a highly potent and specific inhibitor of TLR8. A successful solution of the X-ray crystal structure of TLR8 in complex with TH1027 provided an in-depth mechanistic insight into its binding mode, validating that TH1027 was located between two TLR8 monomers and recognized as an unconventional pocket, thereby preventing TLR8 from activation. Further biological evaluations showed that TH1027 dose-dependently suppressed the TLR8-mediated inflammatory responses in both human monocyte cell lines, peripheral blood mononuclear cells, and rheumatoid arthritis patient specimens, suggesting a strong therapeutic potential against autoimmune diseases. | ||
| + | |||
| + | Rationally Designed Small-Molecule Inhibitors Targeting an Unconventional Pocket on the TLR8 Protein-Protein Interface.,Jiang S, Tanji H, Yin K, Zhang S, Sakaniwa K, Huang J, Yang Y, Li J, Ohto U, Shimizu T, Yin H J Med Chem. 2020 Apr 23;63(8):4117-4132. doi: 10.1021/acs.jmedchem.9b02128. Epub , 2020 Apr 13. PMID:32233366<ref>PMID:32233366</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6kya" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Ohto U]] | [[Category: Ohto U]] | ||
Revision as of 10:46, 22 November 2023
Crystal structure of human TLR8 in complex TH1027
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