4txz
From Proteopedia
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==Crystal structure of Vibrio cholerae DncV cyclic AMP-GMP synthase in complex with nonhydrolyzable GTP== | ==Crystal structure of Vibrio cholerae DncV cyclic AMP-GMP synthase in complex with nonhydrolyzable GTP== | ||
| - | <StructureSection load='4txz' size='340' side='right' caption='[[4txz]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='4txz' size='340' side='right'caption='[[4txz]], [[Resolution|resolution]] 2.80Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[4txz]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TXZ OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[4txz]] 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=4TXZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TXZ FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> |
| - | <tr><td class="sblockLbl"><b> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G2P:PHOSPHOMETHYLPHOSPHONIC+ACID+GUANYLATE+ESTER'>G2P</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4txz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4txz OCA], [https://pdbe.org/4txz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4txz RCSB], [https://www.ebi.ac.uk/pdbsum/4txz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4txz ProSAT]</span></td></tr> |
| - | <table> | + | </table> |
| + | == Function == | ||
| + | [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;"> | ||
| + | == 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. | ||
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| + | 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> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4txz" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[Cyclic GMP-AMP synthase 3D synthase|Cyclic GMP-AMP synthase 3D synthase]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Vibrio cholerae O1 biovar El Tor str. N16961]] |
| - | [[Category: | + | [[Category: Berger JM]] |
| - | [[Category: | + | [[Category: Doudna JA]] |
| - | [[Category: | + | [[Category: Kranzusch PJ]] |
| - | [[Category: | + | [[Category: Lee ASY]] |
| - | [[Category: | + | [[Category: Solovykh MS]] |
| - | [[Category: | + | [[Category: Vance RE]] |
| - | [[Category: | + | [[Category: Wilson SC]] |
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Current revision
Crystal structure of Vibrio cholerae DncV cyclic AMP-GMP synthase in complex with nonhydrolyzable GTP
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