View source for 9c3g


==human cGAS core domain (K427E/K428E) bound to Cladophorol A==
<StructureSection load='9c3g' size='340' side='right'caption='[[9c3g]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9c3g]] 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=9C3G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9C3G 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]] 2.75&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1AVI:2,3,8,9-tetrakis(oxidanyl)benzo[c]chromen-6-one'>A1AVI</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=9c3g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9c3g OCA], [https://pdbe.org/9c3g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9c3g RCSB], [https://www.ebi.ac.uk/pdbsum/9c3g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9c3g ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CGAS_HUMAN CGAS_HUMAN] Nucleotidyltransferase that catalyzes formation of cyclic GMP-AMP (cGAMP) from ATP and GTP and exhibits antiviral activity. Has antiviral activity by acting as a key cytosolic DNA sensor, the presence of DNA in the cytoplasm being a danger signal that triggers the immune responses. Binds cytosolic DNA directly, leading to activation and synthesis of cGAMP, a second messenger that binds to and activates TMEM173/STING, thereby triggering type-I interferon production.<ref>PMID:21478870</ref> <ref>PMID:23258413</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS) is an enzyme sensor of double-stranded DNA (dsDNA) that serves to trigger activation of the cGAS-stimulator of interferon genes (STING) pathway. Excessive activation of this pathway has been demonstrated to contribute to various forms of inflammatory disease. As such, cGAS has arisen as a potential therapeutic target with broad potential applications. Using a pathway-targeted cell-based screening approach, we identified the natural product Cladophorol-A as a new class of non-cytotoxic cGAS inhibitor (cell-based IC(50) = 370 nM). An X-ray co-crystal structure at 2.75 A resolution revealed that Cladophorol-A inhibits cGAS by binding to its active site within the conserved adenosine nucleobase binding site.

Cladophorol-A is an inhibitor of cyclic GMP-AMP synthase.,Kissai M, Chin EN, Martinez-Pena F, Sulpizio A, Stout EP, Usui I, Barmare F, Sanchez B, Esquenazi E, Stanfield RL, Wilson IA, Lairson LL Bioorg Med Chem Lett. 2025 Jan 1;115:130007. doi: 10.1016/j.bmcl.2024.130007. , Epub 2024 Nov 7. PMID:39521150<ref>PMID:39521150</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9c3g" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kissai M]]
[[Category: Lairson LL]]
[[Category: Stanfield RL]]