View source for 7buq


==mcGAS bound with 23-cGAMP==
<StructureSection load='7buq' size='340' side='right'caption='[[7buq]], [[Resolution|resolution]] 3.09&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7buq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BUQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BUQ 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]] 3.091&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1SY:CGAMP'>1SY</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=7buq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7buq OCA], [https://pdbe.org/7buq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7buq RCSB], [https://www.ebi.ac.uk/pdbsum/7buq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7buq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CGAS_MOUSE CGAS_MOUSE] 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.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
DNA binding allosterically activates the cytosolic DNA sensor cGAS (cyclic GMP-AMP [cGAMP] synthase) to synthesize 2'3'-cGAMP, using Mg(2+) as the metal cofactor that catalyzes two nucleotidyl-transferring reactions. We previously found that Mn(2+) potentiates cGAS activation, but the underlying mechanism remains unclear. Here, we report that Mn(2+) directly activates cGAS. Structural analysis reveals that Mn(2+)-activated cGAS undergoes globally similar conformational changes to DNA-activated cGAS but forms a unique eta1 helix to widen the catalytic pocket, allowing substrate entry and cGAMP synthesis. Strikingly, in Mn(2+)-activated cGAS, the linear intermediates pppGpG and pGpA take an inverted orientation in the active pocket, suggesting a noncanonical but accelerated cGAMP cyclization without substrate flip-over. Moreover, unlike the octahedral coordination around Mg(2+), the two catalytic Mn(2+) are coordinated by triphosphate moiety of the inverted substrate, independent of the catalytic triad residues. Our findings thus uncover Mn(2+) as a cGAS activator that initiates noncanonical 2'3'-cGAMP synthesis.

Mn(2+) Directly Activates cGAS and Structural Analysis Suggests Mn(2+) Induces a Noncanonical Catalytic Synthesis of 2'3'-cGAMP.,Zhao Z, Ma Z, Wang B, Guan Y, Su XD, Jiang Z Cell Rep. 2020 Aug 18;32(7):108053. doi: 10.1016/j.celrep.2020.108053. PMID:32814054<ref>PMID:32814054</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7buq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cyclic GMP-AMP synthase 3D synthase|Cyclic GMP-AMP synthase 3D synthase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Su XD]]
[[Category: Wang B]]