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7crf
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of human TLR8 in complex with CU-CPD107== | |
| + | <StructureSection load='7crf' size='340' side='right'caption='[[7crf]], [[Resolution|resolution]] 2.89Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7crf]] 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=7CRF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CRF 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]] 2.89Å</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=GD0:1-[2-(ethoxymethyl)-4-iodanyl-5-phenyl-imidazol-1-yl]-2-methyl-propan-2-ol'>GD0</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=7crf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7crf OCA], [https://pdbe.org/7crf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7crf RCSB], [https://www.ebi.ac.uk/pdbsum/7crf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7crf ProSAT]</span></td></tr> | ||
| + | </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 == | ||
| + | Small-molecule modulators of TLR8 have drawn much interests as it plays pivotal roles in the innate immune response to single-stranded RNAs (ssRNAs) derived from viruses. However, their clinical uses are limited because they can invoke an uncontrolled, global inflammatory response. The efforts described herein culminate in the fortuitous discovery of a tetrasubstituted imidazole CU-CPD107 which inhibits R848-induced TLR8 signaling. In stark contrast, CU-CPD107 shows unexpected synergistic agonist activities in the presence of ssRNA, while CU-CPD107 alone is unable to influence TLR8 signaling. CU-CPD107's unique, dichotomous behavior sheds light on a way to approach TLR agonists. CU-CPD107 offers the opportunity to avoid the undesired, global inflammation side effects that have rendered imidazoquinolines clinically irrelevant, providing an insight for the development of antiviral drugs. | ||
| - | + | Tetrasubstituted imidazoles as incognito Toll-like receptor 8 a(nta)gonists.,Yang Y, Csakai A, Jiang S, Smith C, Tanji H, Huang J, Jones T, Sakaniwa K, Broadwell L, Shi C, Soti S, Ohto U, Fang Y, Shen S, Deng F, Shimizu T, Yin H Nat Commun. 2021 Jul 16;12(1):4351. doi: 10.1038/s41467-021-24536-4. PMID:34272380<ref>PMID:34272380</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7crf" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Toll-like Receptor 3D structures|Toll-like Receptor 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Ohto U]] | ||
| + | [[Category: Sakaniwa K]] | ||
| + | [[Category: Shimizu T]] | ||
| + | [[Category: Tanji H]] | ||
Current revision
Crystal structure of human TLR8 in complex with CU-CPD107
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