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| | ==crystal structure of cyclic GMP-AMP specifc phosphodiesterases in V.cholerae (V-cGAP3)== | | ==crystal structure of cyclic GMP-AMP specifc phosphodiesterases in V.cholerae (V-cGAP3)== |
| - | <StructureSection load='5z7c' size='340' side='right' caption='[[5z7c]], [[Resolution|resolution]] 2.76Å' scene=''> | + | <StructureSection load='5z7c' size='340' side='right'caption='[[5z7c]], [[Resolution|resolution]] 2.76Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5z7c]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z7C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Z7C FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5z7c]] is a 1 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=5Z7C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5Z7C FirstGlance]. <br> |
| - | </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=5z7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z7c OCA], [http://pdbe.org/5z7c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5z7c RCSB], [http://www.ebi.ac.uk/pdbsum/5z7c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5z7c ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.76Å</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=5z7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z7c OCA], [https://pdbe.org/5z7c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5z7c RCSB], [https://www.ebi.ac.uk/pdbsum/5z7c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5z7c ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CGAP3_VIBCH CGAP3_VIBCH]] Phosphodiesterase (PDE) that catalyzes the hydrolysis of 3'3'-cyclic GMP-AMP (3'3'-cGAMP), leading to linear 5'-pApG. Counteracts the function of the 3'3'-cGAMP synthase DncV, and is involved in the modulation of intracellular 3'3'-cGAMP levels. Enhances bacterial chemotaxis and inhibits intestinal colonization in vivo. Thus exerts a crucial role in regulating bacterial infectivity through catalyzing 3'3'-cGAMP degradation. Is specific for 3'3'-cGAMP since it cannot degrade other cGAMP linkage isomers (3'2'-, 2'3'-, and 2'2'-cGAMPs); is also able to hydrolyze c-di-GMP but not c-di-AMP.<ref>PMID:25837739</ref> | + | [https://www.uniprot.org/uniprot/CGAP3_VIBCH CGAP3_VIBCH] Phosphodiesterase (PDE) that catalyzes the hydrolysis of 3'3'-cyclic GMP-AMP (3'3'-cGAMP), leading to linear 5'-pApG. Counteracts the function of the 3'3'-cGAMP synthase DncV, and is involved in the modulation of intracellular 3'3'-cGAMP levels. Enhances bacterial chemotaxis and inhibits intestinal colonization in vivo. Thus exerts a crucial role in regulating bacterial infectivity through catalyzing 3'3'-cGAMP degradation. Is specific for 3'3'-cGAMP since it cannot degrade other cGAMP linkage isomers (3'2'-, 2'3'-, and 2'2'-cGAMPs); is also able to hydrolyze c-di-GMP but not c-di-AMP.<ref>PMID:25837739</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5z7c" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5z7c" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Deng, M J]] | + | [[Category: Large Structures]] |
| - | [[Category: Su, X D]] | + | [[Category: Vibrio cholerae O1 biovar El Tor str. N16961]] |
| - | [[Category: Ye, Z Y]] | + | [[Category: Deng MJ]] |
| - | [[Category: Cyclic dinucleotide]] | + | [[Category: Su XD]] |
| - | [[Category: Metal binding protein]] | + | [[Category: Ye ZY]] |
| - | [[Category: Phosphodiesterase]]
| + | |
| Structural highlights
Function
CGAP3_VIBCH Phosphodiesterase (PDE) that catalyzes the hydrolysis of 3'3'-cyclic GMP-AMP (3'3'-cGAMP), leading to linear 5'-pApG. Counteracts the function of the 3'3'-cGAMP synthase DncV, and is involved in the modulation of intracellular 3'3'-cGAMP levels. Enhances bacterial chemotaxis and inhibits intestinal colonization in vivo. Thus exerts a crucial role in regulating bacterial infectivity through catalyzing 3'3'-cGAMP degradation. Is specific for 3'3'-cGAMP since it cannot degrade other cGAMP linkage isomers (3'2'-, 2'3'-, and 2'2'-cGAMPs); is also able to hydrolyze c-di-GMP but not c-di-AMP.[1]
Publication Abstract from PubMed
3'3'-cyclic GMP-AMP (3'3'-cGAMP) belongs to a family of the bacterial secondary messenger cyclic dinucleotides. It was first discovered in the Vibrio cholerae seventh pandemic strains and is involved in efficient intestinal colonization and chemotaxis regulation. Phosphodiesterases (PDEs) that degrade 3'3'-cGAMP play important regulatory roles in the relevant signaling pathways, and a previous study has identified three PDEs in V. cholerae, namely, V-cGAP1, V-cGAP2, and V-cGAP3, functioning in 3'3'-cGAMP degradation. We report the crystal structure, biochemical, and structural analyses of V-cGAP3, providing a foundation for understanding the mechanism of 3'3'-cGAMP degradation and regulation in general. Our crystal and molecular dynamic (MD)-simulated structures revealed that V-cGAP3 contains tandem HD-GYP domains within its N- and C-terminal domains, with similar three-dimensional topologies despite their low-sequence identity. Biochemical and structural analyses showed that the N-terminal domain plays a mechanism of positive regulation for the catalytic C-terminal domain. We also demonstrated that the other homologous Vibrio PDEs, V-cGAP1/2, likely function via a similar mechanism.
Novel Mechanism for Cyclic Dinucleotide Degradation Revealed by Structural Studies of Vibrio Phosphodiesterase V-cGAP3.,Deng MJ, Tao J, E C, Ye ZY, Jiang Z, Yu J, Su XD J Mol Biol. 2018 Dec 7;430(24):5080-5093. doi: 10.1016/j.jmb.2018.10.010. Epub, 2018 Oct 24. PMID:30365951[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gao J, Tao J, Liang W, Zhao M, Du X, Cui S, Duan H, Kan B, Su X, Jiang Z. Identification and characterization of phosphodiesterases that specifically degrade 3'3'-cyclic GMP-AMP. Cell Res. 2015 May;25(5):539-50. doi: 10.1038/cr.2015.40. Epub 2015 Apr 3. PMID:25837739 doi:http://dx.doi.org/10.1038/cr.2015.40
- ↑ Deng MJ, Tao J, E C, Ye ZY, Jiang Z, Yu J, Su XD. Novel Mechanism for Cyclic Dinucleotide Degradation Revealed by Structural Studies of Vibrio Phosphodiesterase V-cGAP3. J Mol Biol. 2018 Dec 7;430(24):5080-5093. doi: 10.1016/j.jmb.2018.10.010. Epub, 2018 Oct 24. PMID:30365951 doi:http://dx.doi.org/10.1016/j.jmb.2018.10.010
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