8si0 - Revision history

OCA at 19:56, 29 May 2024

2024-05-29T19:56:49Z

←Older revision		Revision as of 19:56, 29 May 2024
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	== Function ==		== 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>		[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 ==
		+	cGAS activates innate immune responses against cytosolic double-stranded DNA. Here, by determining crystal structures of cGAS at various reaction stages, we report a unifying catalytic mechanism. apo-cGAS assumes an array of inactive conformations and binds NTPs nonproductively. Dimerization-coupled double-stranded DNA-binding then affixes the active site into a rigid lock for productive metalsubstrate binding. A web-like network of proteinNTP, intra-NTP, and inter-NTP interactions ensures the stepwise synthesis of 2'-5'/3'-5'-linked cGAMP while discriminating against noncognate NTPs and off-pathway intermediates. One divalent metal is sufficient for productive substrate binding, and capturing the second divalent metal is tightly coupled to nucleotide and linkage specificities, a process which manganese is preferred over magnesium by 100-fold. Additionally, we elucidate how mouse cGAS achieves more stringent NTP and linkage specificities than human cGAS. Together, our results reveal that an adaptable, yet precise lock-and-key-like mechanism underpins cGAS catalysis.
		+
		+	The structural basis for 2'-5'/3'-5'-cGAMP synthesis by cGAS.,Wu S, Gabelli SB, Sohn J Nat Commun. 2024 May 13;15(1):4012. doi: 10.1038/s41467-024-48365-3. PMID:38740774<ref>PMID:38740774</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 8si0" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:53, 22 May 2024

2024-05-22T10:53:28Z

←Older revision		Revision as of 10:53, 22 May 2024
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-	'''Unreleased structure'''

-	~~The entry~~ 8si0 is ~~ON HOLD until 2025~~-04-14	+	==Structure of binary complex of human cGAS and bound cGAMP==
-		+	<StructureSection load='8si0' size='340' side='right'caption='[[8si0]], [[Resolution\|resolution]] 2.70Å' scene=''>
-	~~Authors~~: Wu, S., ~~Sohn~~, J.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[8si0]] 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=8SI0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SI0 FirstGlance]. <br>
-	~~Description~~: ~~Structure~~ of ~~binary complex~~ of ~~human cGAS~~ and ~~bound~~ cGAMP	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.7Å</td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<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>
-	[[Category: ~~Wu, S~~]]	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8si0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8si0 OCA], [https://pdbe.org/8si0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8si0 RCSB], [https://www.ebi.ac.uk/pdbsum/8si0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8si0 ProSAT]</span></td></tr>
-	[[Category: Sohn, J]]	+	</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>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Sohn J]]
		+	[[Category: Wu S]]

OCA at 02:43, 25 May 2023

2023-05-25T02:43:32Z

←Older revision		Revision as of 02:43, 25 May 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8si0 is ON HOLD	+	The entry 8si0 is ON HOLD until 2025-04-14

	Authors: Wu, S., Sohn, J.		Authors: Wu, S., Sohn, J.
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	Description: Structure of binary complex of human cGAS and bound cGAMP		Description: Structure of binary complex of human cGAS and bound cGAMP
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Sohn, J]]
	[[Category: Wu, S]]		[[Category: Wu, S]]
		+	[[Category: Sohn, J]]

OCA: Protected "8si0" [edit=sysop:move=sysop]

2023-04-26T15:24:53Z

Protected "8si0" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:24, 26 April 2023

OCA: New page: '''Unreleased structure''' The entry 8si0 is ON HOLD Authors: Wu, S., Sohn, J. Description: Structure of binary complex of human cGAS and bound cGAMP [[Category: Unreleased Structures]...

2023-04-26T15:24:52Z

New page: '''Unreleased structure''' The entry 8si0 is ON HOLD Authors: Wu, S., Sohn, J. Description: Structure of binary complex of human cGAS and bound cGAMP [[Category: Unreleased Structures]...

New page

'''Unreleased structure'''

The entry 8si0 is ON HOLD

Authors: Wu, S., Sohn, J.

Description: Structure of binary complex of human cGAS and bound cGAMP
[[Category: Unreleased Structures]]
[[Category: Sohn, J]]
[[Category: Wu, S]]