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| | <StructureSection load='4u03' size='340' side='right'caption='[[4u03]], [[Resolution|resolution]] 2.04Å' scene=''> | | <StructureSection load='4u03' size='340' side='right'caption='[[4u03]], [[Resolution|resolution]] 2.04Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4u03]] 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=4U03 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U03 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4u03]] 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=4U03 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U03 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TLL:N-[4-({[(6S)-2-AMINO-5-METHYL-4-OXO-1,4,5,6,7,8-HEXAHYDROPTERIDIN-6-YL]METHYL}AMINO)BENZOYL]-L-GAMMA-GLUTAMYL-L-GLUTAMIC+ACID'>TLL</scene></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]] 2.041Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4u0l|4u0l]], [[4u0m|4u0m]], [[4u0n|4u0n]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TLL:N-[4-({[(6S)-2-AMINO-5-METHYL-4-OXO-1,4,5,6,7,8-HEXAHYDROPTERIDIN-6-YL]METHYL}AMINO)BENZOYL]-L-GAMMA-GLUTAMYL-L-GLUTAMIC+ACID'>TLL</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=4u03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u03 OCA], [https://pdbe.org/4u03 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4u03 RCSB], [https://www.ebi.ac.uk/pdbsum/4u03 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4u03 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=4u03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u03 OCA], [http://pdbe.org/4u03 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4u03 RCSB], [http://www.ebi.ac.uk/pdbsum/4u03 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4u03 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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| | ==See Also== | | ==See Also== |
| - | *[[Cyclic GMP-AMP synthase|Cyclic GMP-AMP synthase]] | + | *[[Cyclic GMP-AMP synthase 3D synthase|Cyclic GMP-AMP synthase 3D synthase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __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: Xiang, Y]] | + | [[Category: Xiang Y]] |
| - | [[Category: Zhu, D Y]] | + | [[Category: Zhu DY]] |
| - | [[Category: Regulation]]
| + | |
| - | [[Category: Transferase]]
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| 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 are a newly expanded class of second messengers that contribute to the regulation of multiple different pathways in bacterial, eukaryotic, and archaeal cells. The recently identified Vibrio cholerae dinucleotide cyclase (DncV, the gene product of VC0179) can generate three different cyclic dinucleotides and preferentially synthesize a hybrid cyclic-GMP-AMP. Here, we report the crystal structural and functional studies of DncV. We unexpectedly observed a 5-methyltetrahydrofolate diglutamate (5MTHFGLU2) molecule bound in a surface pocket opposite the nucleotide substrate-binding groove of DncV. Subsequent mutagenesis and functional studies showed that the enzymatic activity of DncV is regulated by folate-like molecules, suggesting the existence of a signaling pathway that links folate-like metabolism cofactors to the regulation of cyclic dinucleotide second messenger synthesis. Sequence analysis showed that the residues involved in 5MTHFGLU2 binding are highly conserved in DncV orthologs, implying the presence of this regulation mechanism in a wide variety of bacteria.
Structural Biochemistry of a Vibrio cholerae Dinucleotide Cyclase Reveals Cyclase Activity Regulation by Folates.,Zhu D, Wang L, Shang G, Liu X, Zhu J, Lu D, Wang L, Kan B, Zhang JR, Xiang Y Mol Cell. 2014 Sep 18;55(6):931-7. doi: 10.1016/j.molcel.2014.08.001. Epub 2014, Sep 4. PMID:25201413[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhu D, Wang L, Shang G, Liu X, Zhu J, Lu D, Wang L, Kan B, Zhang JR, Xiang Y. Structural Biochemistry of a Vibrio cholerae Dinucleotide Cyclase Reveals Cyclase Activity Regulation by Folates. Mol Cell. 2014 Sep 18;55(6):931-7. doi: 10.1016/j.molcel.2014.08.001. Epub 2014, Sep 4. PMID:25201413 doi:http://dx.doi.org/10.1016/j.molcel.2014.08.001
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