View source for 6ydb


==Human wtSTING in complex with 2',2'-difluoro-3',3'-c-di-GMP==
<StructureSection load='6ydb' size='340' side='right'caption='[[6ydb]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ydb]] 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=6YDB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YDB 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]] 2.801&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GGF:2-azanyl-9-[(1~{R},6~{R},8~{R},9~{R},10~{R},15~{R},17~{R},18~{R})-17-(2-azanyl-6-oxidanylidene-1~{H}-purin-9-yl)-9,18-bis(fluoranyl)-3,12-bis(oxidanyl)-3,12-bis(oxidanylidene)-2,4,7,11,13,16-hexaoxa-3$l^{5},12$l^{5}-diphosphatricyclo[13.3.0.0^{6,10}]octadecan-8-yl]-1~{H}-purin-6-one'>GGF</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=6ydb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ydb OCA], [https://pdbe.org/6ydb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ydb RCSB], [https://www.ebi.ac.uk/pdbsum/6ydb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ydb ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/STING_HUMAN STING_HUMAN] Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm. Acts by recognizing and binding cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic GMP-AMP (cGAMP), a messenger produced in response to DNA virus in the cytosol: upon binding of c-di-GMP or cGAMP, autoinhibition is alleviated and TMEM173/STING is able to activate both NF-kappa-B and IRF3 transcription pathways to induce expression of type I interferon and exert a potent anti-viral state. May be involved in translocon function, the translocon possibly being able to influence the induction of type I interferons. May be involved in transduction of apoptotic signals via its association with the major histocompatibility complex class II (MHC-II). Mediates death signaling via activation of the extracellular signal-regulated kinase (ERK) pathway.<ref>PMID:18818105</ref> <ref>PMID:18724357</ref> <ref>PMID:19776740</ref> <ref>PMID:19433799</ref> <ref>PMID:21074459</ref> <ref>PMID:21947006</ref> <ref>PMID:23258412</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
STING (stimulator of interferon genes) is a key regulator of innate immunity that has recently been recognized as a promising drug target. STING is activated by cyclic dinucleotides (CDNs) which eventually leads to expression of type I interferons and other cytokines. Factors underlying the affinity of various CDN analogues are poorly understood. Herein, we correlate structural biology, isothermal calorimetry (ITC) and computational modeling to elucidate factors contributing to binding of six CDNs-three pairs of natural (ribo) and fluorinated (2'-fluororibo) 3',3'-CDNs. X-ray structural analyses of six {STING:CDN} complexes did not offer any explanation for the different affinities of the studied ligands. ITC showed entropy/enthalpy compensation up to 25 kcal mol(-1) for this set of similar ligands. The higher affinities of fluorinated analogues are explained with help of computational methods by smaller loss of entropy upon binding and by smaller strain (free) energy.

Ligand Strain and Its Conformational Complexity Is a Major Factor in the Binding of Cyclic Dinucleotides to STING Protein.,Smola M, Gutten O, Dejmek M, Kozisek M, Evangelidis T, Tehrani ZA, Novotna B, Nencka R, Birkus G, Rulisek L, Boura E Angew Chem Int Ed Engl. 2021 Feb 22. doi: 10.1002/anie.202016805. PMID:33616279<ref>PMID:33616279</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ydb" style="background-color:#fffaf0;"></div>

==See Also==
*[[Stimulator of interferon genes protein 3D structures|Stimulator of interferon genes protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Boura E]]
[[Category: Smola M]]