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| | <StructureSection load='6v9u' size='340' side='right'caption='[[6v9u]], [[Resolution|resolution]] 2.65Å' scene=''> | | <StructureSection load='6v9u' size='340' side='right'caption='[[6v9u]], [[Resolution|resolution]] 2.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6v9u]] is a 2 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=6V9U OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6V9U FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6v9u]] 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=6V9U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V9U FirstGlance]. <br> |
| - | </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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=QSM:2-(3,4-dimethoxyphenyl)-5-(piperidin-4-yl)-3-(propan-2-yl)-1H-indole'>QSM</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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]] 2.65Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TLR8, UNQ249/PRO286 ([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=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=QSM:2-(3,4-dimethoxyphenyl)-5-(piperidin-4-yl)-3-(propan-2-yl)-1H-indole'>QSM</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6v9u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v9u OCA], [http://pdbe.org/6v9u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6v9u RCSB], [http://www.ebi.ac.uk/pdbsum/6v9u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6v9u 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=6v9u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v9u OCA], [https://pdbe.org/6v9u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v9u RCSB], [https://www.ebi.ac.uk/pdbsum/6v9u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v9u ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6v9u" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6v9u" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Toll-like Receptor 3D structures|Toll-like Receptor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Critton, D A]] | + | [[Category: Critton DA]] |
| - | [[Category: Endosomal receptor]]
| + | |
| - | [[Category: Innate immunity]]
| + | |
| - | [[Category: Pathogen-associated molecular pattern]]
| + | |
| - | [[Category: Pattern recognition receptor]]
| + | |
| - | [[Category: Rna binding protein]]
| + | |
| - | [[Category: Toll-like receptor]]
| + | |
| Structural highlights
Function
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.[1]
Publication Abstract from PubMed
The toll-like receptor (TLR) family is an evolutionarily conserved component of the innate immune system, responsible for the early detection of foreign or endogenous threat signals. In the context of autoimmunity, the unintended recognition of self-motifs as foreign promotes initiation or propagation of disease. Overactivation of TLR7 and TLR9 have been implicated as factors contributing to autoimmune disorders such as psoriasis, arthritis, and lupus. In our search for small molecule antagonists of TLR7/9, 7f was identified as possessing excellent on-target potency for human TLR7/9 as well as for TLR8, with selectivity against other representative TLR family members. Good pharmacokinetic properties and a relatively balanced potency against TLR7 and TLR9 in mouse systems (systems which lack functional TLR8) made this an excellent in vivo tool compound, and efficacy from oral dosing in preclinical models of autoimmune disease was demonstrated.
Discovery of Potent and Orally Bioavailable Small Molecule Antagonists of Toll-like Receptors 7/8/9 (TLR7/8/9).,Mussari CP, Dodd DS, Sreekantha RK, Pasunoori L, Wan H, Posy SL, Critton D, Ruepp S, Subramanian M, Watson A, Davies P, Schieven GL, Salter-Cid LM, Srivastava R, Tagore DM, Dudhgaonkar S, Poss MA, Carter PH, Dyckman AJ ACS Med Chem Lett. 2020 Jul 29;11(9):1751-1758. doi:, 10.1021/acsmedchemlett.0c00264. eCollection 2020 Sep 10. PMID:32944143[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Doyle SL, Jefferies CA, Feighery C, O'Neill LA. Signaling by Toll-like receptors 8 and 9 requires Bruton's tyrosine kinase. J Biol Chem. 2007 Dec 21;282(51):36953-60. Epub 2007 Oct 11. PMID:17932028 doi:10.1074/jbc.M707682200
- ↑ Mussari CP, Dodd DS, Sreekantha RK, Pasunoori L, Wan H, Posy SL, Critton D, Ruepp S, Subramanian M, Watson A, Davies P, Schieven GL, Salter-Cid LM, Srivastava R, Tagore DM, Dudhgaonkar S, Poss MA, Carter PH, Dyckman AJ. Discovery of Potent and Orally Bioavailable Small Molecule Antagonists of Toll-like Receptors 7/8/9 (TLR7/8/9). ACS Med Chem Lett. 2020 Jul 29;11(9):1751-1758. doi:, 10.1021/acsmedchemlett.0c00264. eCollection 2020 Sep 10. PMID:32944143 doi:http://dx.doi.org/10.1021/acsmedchemlett.0c00264
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