View source for 6lvy


==Crystal structure of TLR7/Cpd-2 (SM-360320) complex==
<StructureSection load='6lvy' size='340' side='right'caption='[[6lvy]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6lvy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Macaca_mulatta Macaca mulatta]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LVY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LVY 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EWU:6-azanyl-2-(2-methoxyethoxy)-9-(phenylmethyl)-7H-purin-8-one'>EWU</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6lvy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lvy OCA], [https://pdbe.org/6lvy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lvy RCSB], [https://www.ebi.ac.uk/pdbsum/6lvy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lvy ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/B3Y653_MACMU B3Y653_MACMU] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Toll-like receptor 7 (TLR7) recognizes both microbial and endogenous RNAs and nucleosides. Aberrant activation of TLR7 has been implicated in several autoimmune diseases including systemic lupus erythematosus (SLE). Here, by modifying potent TLR7 agonists, we develop a series of TLR7-specific antagonists as promising therapeutic agents for SLE. These compounds protect mice against lethal autoimmunity. Combining crystallography and cryo-electron microscopy, we identify the open conformation of the receptor and reveal the structural equilibrium between open and closed conformations that underlies TLR7 antagonism, as well as the detailed mechanism by which TLR7-specific antagonists bind to their binding pocket in TLR7. Our work provides small-molecule TLR7-specific antagonists and suggests the TLR7-targeting strategy for treating autoimmune diseases.

Structural analysis reveals TLR7 dynamics underlying antagonism.,Tojo S, Zhang Z, Matsui H, Tahara M, Ikeguchi M, Kochi M, Kamada M, Shigematsu H, Tsutsumi A, Adachi N, Shibata T, Yamamoto M, Kikkawa M, Senda T, Isobe Y, Ohto U, Shimizu T Nat Commun. 2020 Oct 15;11(1):5204. doi: 10.1038/s41467-020-19025-z. PMID:33060576<ref>PMID:33060576</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6lvy" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Macaca mulatta]]
[[Category: Ohto U]]
[[Category: Shimizu T]]
[[Category: Zhang Z]]