5vdt: Difference between revisions
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<StructureSection load='5vdt' size='340' side='right' caption='[[5vdt]], [[Resolution|resolution]] 2.58Å' scene=''> | <StructureSection load='5vdt' size='340' side='right' caption='[[5vdt]], [[Resolution|resolution]] 2.58Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5vdt]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VDT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VDT FirstGlance]. <br> | <table><tr><td colspan='2'>[[5vdt]] 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=5VDT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VDT FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4BW:2-AMINO-9-[(2R,3R,3AS,5R,7AR,9R,10R,10AS,12R,14AR)-9-(6-AMINO-9H-PURIN-9-YL)-3,5,10,12-TETRAHYDROXY-5,12-DIOXIDOOCTAHYDRO-2H,7H-DIFURO[3,2-D 3,2-J][1,3,7,9,2,8]TETRAOXADIPHOSPHACYCLODODECIN-2-YL]-1,9-DIHYDRO-6H-PURIN-6-ONE'>4BW</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4BW:2-AMINO-9-[(2R,3R,3AS,5R,7AR,9R,10R,10AS,12R,14AR)-9-(6-AMINO-9H-PURIN-9-YL)-3,5,10,12-TETRAHYDROXY-5,12-DIOXIDOOCTAHYDRO-2H,7H-DIFURO[3,2-D 3,2-J][1,3,7,9,2,8]TETRAOXADIPHOSPHACYCLODODECIN-2-YL]-1,9-DIHYDRO-6H-PURIN-6-ONE'>4BW</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]], [[5vdp|5vdp]], [[5vdq|5vdq]], [[5vdr|5vdr]], [[5vds|5vds]], [[5vdu|5vdu]], [[5vdv|5vdv]], [[5vdw|5vdw]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5vdo|5vdo]], [[5vdp|5vdp]], [[5vdq|5vdq]], [[5vdr|5vdr]], [[5vds|5vds]], [[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='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=5vdt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vdt OCA], [http://pdbe.org/5vdt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vdt RCSB], [http://www.ebi.ac.uk/pdbsum/5vdt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vdt ProSAT]</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=5vdt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vdt OCA], [http://pdbe.org/5vdt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vdt RCSB], [http://www.ebi.ac.uk/pdbsum/5vdt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vdt ProSAT]</span></td></tr> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Cyclic GMP-AMP synthase]] | [[Category: Cyclic GMP-AMP synthase]] | ||
[[Category: Human]] | |||
[[Category: Byrnes, L J]] | [[Category: Byrnes, L J]] | ||
[[Category: Hall, J D]] | [[Category: Hall, J D]] | ||
Revision as of 10:48, 6 December 2017
Human cyclic GMP-AMP synthase (cGAS) in complex with 3',3'-cGAMPHuman cyclic GMP-AMP synthase (cGAS) in complex with 3',3'-cGAMP
Structural highlights
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 PubMedCyclic 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
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