3wn4: Difference between revisions

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-{{STRUCTURE_3wn4|  PDB=3wn4  |  SCENE=  }}
+==Crystal structure of human TLR8 in complex with DS-877==
-===Crystal structure of human TLR8 in complex with DS-877===
+<StructureSection load='3wn4' size='340' side='right' caption='[[3wn4]], [[Resolution|resolution]] 1.81&Aring;' scene=''>
-{{ABSTRACT_PUBMED_24474703}}
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3wn4]] is a 1 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=3WN4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WN4 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=D87:2-BUTYLFURO[2,3-C]QUINOLIN-4-AMINE'>D87</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></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='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=3wn4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wn4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3wn4 RCSB], [http://www.ebi.ac.uk/pdbsum/3wn4 PDBsum]</span></td></tr>
+</table>
+== 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>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Toll-like receptor (TLR)-8 agonists activate adaptive immune responses by inducing robust production of T helper 1-polarizing cytokines, suggesting that TLR8-active compounds might be promising candidate vaccine adjuvants. Recently, a C2-butyl furo[2,3-c]quinoline was reported with purely TLR8 agonistic activity. This compound was successfully co-crystallized with the human TLR8 ectodomain, and the co-crystal structure revealed ligand-induced reorganization of the binding pocket of TLR8. The loss of a key hydrogen bond between the oxygen atom of the furanyl ring of the agonist and Thr 574 in TLR8 suggested that the furan ring is dispensable. Employing a disconnection strategy, 3- and 4-substituted aminoquinolines were investigated. Focused structure-based ligand design studies led to the identification of 3-pentyl-quinoline-2-amine as a novel, structurally simple, and highly potent human TLR8-specific agonist (EC50 =0.2 muM). Preliminary evaluation of this compound in ex vivo human blood assay systems revealed that it retains prominent cytokine-inducing activity. Together, these results indicate the suitability of this compound as a novel vaccine adjuvant, warranting further investigation.
-==Function==
+Structure-Based Design of Novel Human Toll-like Receptor 8 Agonists.,Kokatla HP, Sil D, Tanji H, Ohto U, Malladi SS, Fox LM, Shimizu T, David SA ChemMedChem. 2014 Jan 28. doi: 10.1002/cmdc.201300573. PMID:24474703<ref>PMID:24474703</ref>
-[[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>
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[3wn4]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WN4 OCA].
+</div>
-==Reference==
+==See Also==
-<ref group="xtra">PMID:024474703</ref><references group="xtra"/><references/>
+*[[Toll-like Receptors|Toll-like Receptors]]
-[[Category: Ohto, U.]]
+== References ==
-[[Category: Shimizu, T.]]
+<references/>
-[[Category: Tanji, H.]]
+__TOC__
+</StructureSection>
+[[Category: Human]]
+[[Category: Ohto, U]]
+[[Category: Shimizu, T]]
+[[Category: Tanji, H]]
 [[Category: Antiviral-antitumor drug binding]]
 [[Category: Glycosylation]]