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4txy

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Revision as of 17:13, 11 August 2016

Crystal structure of Vibrio cholerae DncV cyclic AMP-GMP synthase, a prokaryotic cGAS homolog

Structural highlights

4txy is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Activity:	Cyclic GMP-AMP synthase, with EC number 2.7.7.86
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.

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^[1]

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

References

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

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4txy"

@@ Line 1: / Line 1: @@
 ==Crystal structure of Vibrio cholerae DncV cyclic AMP-GMP synthase, a prokaryotic cGAS homolog==
 <StructureSection load='4txy' size='340' side='right' caption='[[4txy]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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=4txy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4txy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4txy RCSB], [http://www.ebi.ac.uk/pdbsum/4txy PDBsum]</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=4txy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4txy OCA], [http://pdbe.org/4txy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4txy RCSB], [http://www.ebi.ac.uk/pdbsum/4txy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4txy ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4txy" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Cyclic GMP-AMP synthase|Cyclic GMP-AMP synthase]]
 == References ==
 <references/>

4txy

From Proteopedia

Revision as of 17:13, 11 August 2016

Crystal structure of Vibrio cholerae DncV cyclic AMP-GMP synthase, a prokaryotic cGAS homolog

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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