4qxr: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4qxr]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QXR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QXR FirstGlance]. <br> | <table><tr><td colspan='2'>[[4qxr]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QXR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QXR FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1YE:(5,6-DIMETHYL-9-OXO-9H-XANTHEN-4-YL)ACETIC+ACID'>1YE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>< | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1YE:(5,6-DIMETHYL-9-OXO-9H-XANTHEN-4-YL)ACETIC+ACID'>1YE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4qxo|4qxo]], [[4qxp|4qxp]], [[4qxq|4qxq]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4qxo|4qxo]], [[4qxp|4qxp]], [[4qxq|4qxq]]</td></tr> | ||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4qxr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qxr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qxr RCSB], [http://www.ebi.ac.uk/pdbsum/4qxr PDBsum]</span></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=4qxr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qxr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qxr RCSB], [http://www.ebi.ac.uk/pdbsum/4qxr PDBsum]</span></td></tr> | ||
<table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
Revision as of 08:38, 8 October 2014
Crystal structure of hSTING(S162A/G230I/Q266I) in complex with DMXAACrystal structure of hSTING(S162A/G230I/Q266I) in complex with DMXAA
Structural highlights
Publication Abstract from PubMedThe drug DMXAA (5,6-dimethylxanthenone-4-acetic acid) showed therapeutic promise against solid tumors in mouse models but subsequently failed in human clinical trials. DMXAA was later discovered to activate mouse, but not human, STING, an adaptor protein in the cyclic dinucleotide cGAMP-mediated signaling pathway, inducing type I interferon expression. To facilitate the development of compounds that target human STING, we combined structural, biophysical, and cellular assays to study mouse and human chimeric proteins and their interaction with DMXAA. We identified a single substitution (G230I) that enables a DMXAA-induced conformational transition of hSTING from an inactive "open" to an active "closed" state. We also identified a substitution within the binding pocket (Q266I) that cooperates with G230I and the previously identified S162A binding-pocket point substitution, rendering hSTING highly sensitive to DMXAA. These findings should facilitate the reciprocal engineering of DMXAA analogs that bind and stimulate wild-type hSTING and their exploitation for vaccine-adjuvant and anticancer drug development. Binding-Pocket and Lid-Region Substitutions Render Human STING Sensitive to the Species-Specific Drug DMXAA.,Gao P, Zillinger T, Wang W, Ascano M, Dai P, Hartmann G, Tuschl T, Deng L, Barchet W, Patel DJ Cell Rep. 2014 Sep 3. pii: S2211-1247(14)00673-1. doi:, 10.1016/j.celrep.2014.08.010. PMID:25199835[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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