View source for 5awa


==Crystal structure of human TLR8 in complex with MB-568==
<StructureSection load='5awa' size='340' side='right'caption='[[5awa]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5awa]] is a 1 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=5AWA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AWA 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]] 2.2&#8491;</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=M8D:5-[[3-(AMINOMETHYL)PHENYL]METHYL]-3-PENTYL-QUINOLIN-2-AMINE'>M8D</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=5awa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5awa OCA], [https://pdbe.org/5awa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5awa RCSB], [https://www.ebi.ac.uk/pdbsum/5awa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5awa 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> 
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== Publication Abstract from PubMed ==
Human Toll-like receptor 8 (hTLR8) is expressed in myeloid dendritic cells, monocytes, and monocyte-derived dendritic cells. Engagement by TLR8 agonists evokes a distinct cytokine profile which favors the development of type 1 helper T cells. Crystal structures of the ectodomain of hTLR8 cocrystallized with two regioisomers of a dual TLR7/8-agonistic N1-substituted imidazoquinolines showed subtle differences in their interactions in the binding site of hTLR8. We hypothesized that the potency of a previously reported best-in-class pure TLR8 agonist, 3-pentylquinoline-2-amine, could be further enhanced by "designing in" functional groups that would mimic key intermolecular interactions that we had observed in the crystal structures. We performed a focused exploration of decorating the quinoline core with alkylamino groups at all possible positions. These studies have led to the identification of a novel TLR8 agonist that was approximately 20-fold more potent than the parent compound and displays prominent adjuvantic activity in a rabbit model of immunization.

Structure-Based Design of Human TLR8-Specific Agonists with Augmented Potency and Adjuvanticity.,Beesu M, Caruso G, Salyer AC, Khetani KK, Sil D, Weerasinghe M, Tanji H, Ohto U, Shimizu T, David SA J Med Chem. 2015 Oct 8;58(19):7833-49. doi: 10.1021/acs.jmedchem.5b01087. Epub, 2015 Sep 22. PMID:26351878<ref>PMID:26351878</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5awa" 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: Shimizu T]]
[[Category: Tanji H]]