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| | <StructureSection load='4txy' size='340' side='right'caption='[[4txy]], [[Resolution|resolution]] 3.00Å' scene=''> | | <StructureSection load='4txy' size='340' side='right'caption='[[4txy]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4txy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Vibch Vibch]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TXY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TXY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4txy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Vibrio_cholerae_O1_biovar_El_Tor_str._N16961 Vibrio cholerae O1 biovar El Tor str. N16961]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TXY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TXY FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dncV, VC_0179 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=243277 VIBCH])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4txy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4txy OCA], [https://pdbe.org/4txy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4txy RCSB], [https://www.ebi.ac.uk/pdbsum/4txy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4txy ProSAT]</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=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> | | </table> |
| | == Function == | | == 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. | + | [https://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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Cyclic GMP-AMP synthase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Vibch]] | + | [[Category: Vibrio cholerae O1 biovar El Tor str. N16961]] |
| - | [[Category: Berger, J M]] | + | [[Category: Berger JM]] |
| - | [[Category: Doudna, J A]] | + | [[Category: Doudna JA]] |
| - | [[Category: Kranzusch, P J]] | + | [[Category: Kranzusch PJ]] |
| - | [[Category: Lee, A S.Y]] | + | [[Category: Lee ASY]] |
| - | [[Category: Solovykh, M S]] | + | [[Category: Solovykh MS]] |
| - | [[Category: Vance, R E]] | + | [[Category: Vance RE]] |
| - | [[Category: Wilson, S C]] | + | [[Category: Wilson SC]] |
| - | [[Category: Cga]]
| + | |
| - | [[Category: Cyclic nucleotide synthase]]
| + | |
| - | [[Category: Nucleotidyl transferase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
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.
See Also
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
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