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5vdp

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Revision as of 07:48, 6 December 2017

Human cyclic GMP-AMP synthase (cGAS) in complex with 2',3'-cGAMP

Structural highlights

5vdp is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	5vdo, 5vdq, 5vdr, 5vds, 5vdt, 5vdu, 5vdv, 5vdw
Gene:	MB21D1, C6orf150 (HUMAN)
Activity:	Cyclic GMP-AMP synthase, with EC number 2.7.7.86
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2]

Publication Abstract from PubMed

Cyclic GMP-AMP synthase (cGAS) is activated by ds-DNA binding to produce the secondary messenger 2',3'-cGAMP. cGAS is an important control point in the innate immune response; dysregulation of the cGAS pathway is linked to autoimmune diseases while targeted stimulation may be of benefit in immunoncology. We report here the structure of cGAS with dinucleotides and small molecule inhibitors, and kinetic studies of the cGAS mechanism. Our structural work supports the understanding of how ds-DNA activates cGAS, suggesting a site for small molecule binders that may cause cGAS activation at physiological ATP concentrations, and an apparent hotspot for inhibitor binding. Mechanistic studies of cGAS provide the first kinetic constants for 2',3'-cGAMP formation, and interestingly, describe a catalytic mechanism where 2',3'-cGAMP may be a minor product of cGAS compared to linear nucleotides. This article is protected by copyright. All rights reserved.

The catalytic mechanism of cyclic gmp-amp synthase (cGAS) and implications for innate immunity and inhibition.,Hall J, Ralph EC, Shanker S, Wang H, Byrnes LJ, Horst R, Wong J, Brault A, Dumlao D, Smith JF, Dakin LA, Schmitt DC, Trujillo J, Vincent F, Griffor M, Aulabaugh AE Protein Sci. 2017 Sep 22. doi: 10.1002/pro.3304. PMID:28940468^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Schoggins JW, Wilson SJ, Panis M, Murphy MY, Jones CT, Bieniasz P, Rice CM. A diverse range of gene products are effectors of the type I interferon antiviral response. Nature. 2011 Apr 28;472(7344):481-5. doi: 10.1038/nature09907. Epub 2011 Apr 10. PMID:21478870 doi:10.1038/nature09907
↑ Sun L, Wu J, Du F, Chen X, Chen ZJ. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science. 2013 Feb 15;339(6121):786-91. doi: 10.1126/science.1232458. Epub 2012, Dec 20. PMID:23258413 doi:10.1126/science.1232458
↑ Hall J, Ralph EC, Shanker S, Wang H, Byrnes LJ, Horst R, Wong J, Brault A, Dumlao D, Smith JF, Dakin LA, Schmitt DC, Trujillo J, Vincent F, Griffor M, Aulabaugh AE. The catalytic mechanism of cyclic gmp-amp synthase (cGAS) and implications for innate immunity and inhibition. Protein Sci. 2017 Sep 22. doi: 10.1002/pro.3304. PMID:28940468 doi:http://dx.doi.org/10.1002/pro.3304

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5vdp"

@@ Line 3: / Line 3: @@
 <StructureSection load='5vdp' size='340' side='right' caption='[[5vdp]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5vdp]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VDP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VDP FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5vdp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VDP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VDP FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1SY:CGAMP'>1SY</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5vdo|5vdo]], [[5vdq|5vdq]], [[5vdr|5vdr]], [[5vds|5vds]], [[5vdt|5vdt]], [[5vdu|5vdu]], [[5vdv|5vdv]], [[5vdw|5vdw]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MB21D1, C6orf150 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cyclic_GMP-AMP_synthase Cyclic GMP-AMP synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.86 2.7.7.86] </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=5vdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vdp OCA], [http://pdbe.org/5vdp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vdp RCSB], [http://www.ebi.ac.uk/pdbsum/5vdp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vdp ProSAT]</span></td></tr>
@@ Line 25: / Line 26: @@
 </StructureSection>
 [[Category: Cyclic GMP-AMP synthase]]
+[[Category: Human]]
 [[Category: Byrnes, L J]]
 [[Category: Hall, J D]]

5vdp

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Revision as of 07:48, 6 December 2017

Human cyclic GMP-AMP synthase (cGAS) in complex with 2',3'-cGAMP

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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