View source for 4ty0


==Crystal structure of Vibrio cholerae DncV cyclic AMP-GMP synthase in complex with linear intermediate 5' pppA(3',5')pG==
<StructureSection load='4ty0' size='340' side='right' caption='[[4ty0]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ty0]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TY0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TY0 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=38V:[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3-[[(2R,3S,4R,5R)-5-(2-azanyl-6-oxidanylidene-3H-purin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]oxy-4-oxidanyl-oxolan-2-yl]methoxy-[[oxidanyl(phosphonooxy)phosphoryl]methyl]phosphinic+acid'>38V</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=4ty0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ty0 OCA], [http://pdbe.org/4ty0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ty0 RCSB], [http://www.ebi.ac.uk/pdbsum/4ty0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ty0 ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/DNCV_VIBCH DNCV_VIBCH]] Catalyzes the synthesis of cyclic AMP-GMP from ATP and GTP. Is also able to produce c-di-AMP and c-di-GMP from ATP and GTP, respectively; however, c-AMP-GMP is the dominant molecule produced by DncV in vivo. Is required for efficient V.cholerae intestinal colonization, and down-regulates the colonization-influencing process of chemotaxis. Is not active with dATP, TTP, UTP, and CTP. 
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== Publication Abstract from PubMed ==
Cyclic dinucleotides (CDNs) play central roles in bacterial pathogenesis and innate immunity. The mammalian enzyme cGAS synthesizes a unique cyclic dinucleotide (cGAMP) containing a 2'-5' phosphodiester linkage essential for optimal immune stimulation, but the molecular basis for linkage specificity is unknown. Here, we show that the Vibrio cholerae pathogenicity factor DncV is a prokaryotic cGAS-like enzyme whose activity provides a mechanistic rationale for the unique ability of cGAS to produce 2'-5' cGAMP. Three high-resolution crystal structures show that DncV and human cGAS generate CDNs in sequential reactions that proceed in opposing directions. We explain 2' and 3' linkage specificity and test this model by reprogramming the human cGAS active site to produce 3'-5' cGAMP, leading to selective stimulation of alternative STING adaptor alleles in cells. These results demonstrate mechanistic homology between bacterial signaling and mammalian innate immunity and explain how active site configuration controls linkage chemistry for pathway-specific signaling.

Structure-Guided Reprogramming of Human cGAS Dinucleotide Linkage Specificity.,Kranzusch PJ, Lee AS, Wilson SC, Solovykh MS, Vance RE, Berger JM, Doudna JA Cell. 2014 Aug 28;158(5):1011-21. doi: 10.1016/j.cell.2014.07.028. Epub 2014 Aug , 14. PMID:25131990<ref>PMID:25131990</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4ty0" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cyclic GMP-AMP synthase|Cyclic GMP-AMP synthase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Cyclic GMP-AMP synthase]]
[[Category: Berger, J M]]
[[Category: Doudna, J A]]
[[Category: Kranzusch, P J]]
[[Category: Lee, A S.Y]]
[[Category: Solovykh, M S]]
[[Category: Vance, R E]]
[[Category: Wilson, S C]]
[[Category: Cga]]
[[Category: Cyclic nucleotide synthase]]
[[Category: Nucleotidyl transferase]]
[[Category: Transferase]]