| IED ID | IndEnz0005001173 |
| Enzyme Type ID | lipase001173 |
| Protein Name |
Cyclic GMP-AMP synthase c-GAMP synthase c-GMP-AMP synthase EC 2.7.7.- 3'3'-cGAMP synthase Cyclic AMP-GMP synthase c-AMP-GMP synthase Dinucleotide cyclase DncV |
| Gene Name | dncV VC_0179 |
| Organism | Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961) |
| Taxonomic Lineage | cellular organisms Bacteria Proteobacteria Gammaproteobacteria Vibrionales Vibrionaceae Vibrio Vibrio cholerae Vibrio cholerae O1 Vibrio cholerae O1 biovar El Tor Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961) |
| Enzyme Sequence | MRMTWNFHQYYTNRNDGLMGKLVLTDEEKNNLKALRKIIRLRTRDVFEEAKGIAKAVKKSALTFEIIQEKVSTTQIKHLSDSEQREVAKLIYEMDDDARDEFLGLTPRFWTQGSFQYDTLNRPFQPGQEMDIDDGTYMPMPIFESEPKIGHSLLILLVDASLKSLVAENHGWKFEAKQTCGRIKIEAEKTHIDVPMYAIPKDEFQKKQIALEANRSFVKGAIFESYVADSITDDSETYELDSENVNLALREGDRKWINSDPKIVEDWFNDSCIRIGKHLRKVCRFMKAWRDAQWDVGGPSSISLMAATVNILDSVAHDASDLGETMKIIAKHLPSEFARGVESPDSTDEKPLFPPSYKHGPREMDIMSKLERLPEILSSAESADSKSEALKKINMAFGNRVTNSELIVLAKALPAFAQEPSSASKPEKISSTMVSG |
| Enzyme Length | 436 |
| Uniprot Accession Number | Q9KVG7 |
| Absorption | |
| Active Site | |
| Activity Regulation | ACTIVITY REGULATION: Enzymatic activity of DncV is inhibited by folate-like molecules, such as 5-methyltetrahydrofolate di-glutamate and 5-methyltetrahydrofolate, suggesting the existence of a signaling pathway that links folate-like metabolism cofactors to the regulation of cyclic dinucleotide second messenger synthesis (PubMed:25201413). Lacks a regulatory loop and is constitutively activated (PubMed:25131990). {ECO:0000269|PubMed:25131990, ECO:0000269|PubMed:25201413}. |
| Binding Site | BINDING 182; /note="ATP"; /evidence="ECO:0000269|PubMed:25131990, ECO:0000269|PubMed:25201413, ECO:0007744|PDB:4U0M"; BINDING 259; /note="ATP"; /evidence="ECO:0000269|PubMed:25131990, ECO:0000269|PubMed:25201413, ECO:0007744|PDB:4U03, ECO:0007744|PDB:4XJ3, ECO:0007744|PDB:4XJ4, ECO:0007744|PDB:4XJ5"; BINDING 287; /note="GTP"; /evidence="ECO:0000269|PubMed:25131990, ECO:0000269|PubMed:25201413, ECO:0000269|PubMed:25865248, ECO:0007744|PDB:4U03, ECO:0007744|PDB:4U0M, ECO:0007744|PDB:4XJ3, ECO:0007744|PDB:4XJ4, ECO:0007744|PDB:4XJ5"; BINDING 301; /note="GTP"; /evidence="ECO:0000269|PubMed:25131990, ECO:0000269|PubMed:25201413, ECO:0000269|PubMed:25865248, ECO:0007744|PDB:4U03, ECO:0007744|PDB:4U0M, ECO:0007744|PDB:4XJ3, ECO:0007744|PDB:4XJ4, ECO:0007744|PDB:4XJ5"; BINDING 348; /note="GTP"; /evidence="ECO:0000269|PubMed:25131990, ECO:0000269|PubMed:25201413, ECO:0000269|PubMed:25865248, ECO:0007744|PDB:4U03, ECO:0007744|PDB:4U0M, ECO:0007744|PDB:4XJ3, ECO:0007744|PDB:4XJ5" |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=ATP + GTP = 3',3'-cGAMP + 2 diphosphate; Xref=Rhea:RHEA:35647, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:37565, ChEBI:CHEBI:71501; Evidence={ECO:0000269|PubMed:22500802, ECO:0000269|PubMed:25131990};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35648; Evidence={ECO:0000269|PubMed:22500802}; |
| DNA Binding | |
| EC Number | 2.7.7.- |
| Enzyme Function | FUNCTION: CBASS (cyclic oligonucleotide-based antiphage signaling system) provides immunity against bacteriophage. The CD-NTase protein synthesizes cyclic nucleotides in response to infection; these serve as specific second messenger signals. The signals activate a diverse range of effectors, leading to bacterial cell death and thus abortive phage infection. A type II-A(GA) CBASS system (PubMed:32839535). {ECO:0000269|PubMed:31533127, ECO:0000303|PubMed:32839535}.; FUNCTION: Catalyzes the synthesis of 3'3'-cyclic GMP-AMP (3'3'-cGAMP) from GTP and ATP, a second messenger in cell signal transduction. Is also able to produce c-di-AMP and c-di-GMP from ATP and GTP, respectively; however, 3'3'-cGAMP is the dominant molecule produced by DncV in vivo, contrary to the 2'3'-cGAMP produced by eukaryotes. 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. Controls the activity of cGAMP-activated phospholipase CapV, a patatin-like lipase that is a direct 3',3'-cGAMP receptor encoded in the dncV operon (PubMed:29891656). {ECO:0000269|PubMed:22500802, ECO:0000269|PubMed:25131990, ECO:0000269|PubMed:29891656}.; FUNCTION: Protects E.coli against phage T2 infection. When the CBASS operon (capV-dcnV-cap2-cap3) is introduced in E.coli MG1655 there is a more than 10(3) decrease in the efficiency of T2 plaque formation. Protects 100-fold against phage T5, offers no protection against T7 (PubMed:32544385). When the 4 gene operon capV-dncV-cap2-cap3 is introduced in E.coli MG1655 there is about 100-fold protection against phages P1 and T2 (PubMed:31533127). {ECO:0000269|PubMed:31533127, ECO:0000269|PubMed:32544385}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 112..117; /note="GTP"; /evidence="ECO:0000269|PubMed:25131990, ECO:0000269|PubMed:25201413, ECO:0000269|PubMed:25865248, ECO:0007744|PDB:4U03, ECO:0007744|PDB:4U0M, ECO:0007744|PDB:4XJ3, ECO:0007744|PDB:4XJ4, ECO:0007744|PDB:4XJ5" |
| Features | Beta strand (12); Binding site (5); Chain (1); Helix (20); Metal binding (3); Mutagenesis (9); Nucleotide binding (1); Region (2); Turn (2) |
| Keywords | 3D-structure;ATP-binding;Antiviral defense;GTP-binding;Magnesium;Metal-binding;Nucleotide metabolism;Nucleotide-binding;Nucleotidyltransferase;Reference proteome;Transferase |
| Interact With | |
| Induction | INDUCTION: Expression is repressed by the transcriptional regulator VspR (PubMed:22500802). Part of the CBASS operon consisting of capV-dncV-cap2-cap3 (Probable). {ECO:0000269|PubMed:22500802, ECO:0000305|PubMed:31533127, ECO:0000305|PubMed:32544385}. |
| Subcellular Location | |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (12) |
| Cross Reference PDB | 4TXY; 4TXZ; 4TY0; 4U03; 4U0L; 4U0M; 4U0N; 4XJ1; 4XJ3; 4XJ4; 4XJ5; 5GO3; |
| Mapped Pubmed ID | 25245040; |
| Motif | |
| Gene Encoded By | |
| Mass | 49,363 |
| Kinetics | |
| Metal Binding | METAL 131; /note="Magnesium; catalytic"; /evidence="ECO:0000269|PubMed:25131990, ECO:0000269|PubMed:25201413, ECO:0000269|PubMed:25865248, ECO:0007744|PDB:4TXY, ECO:0007744|PDB:4TXZ, ECO:0007744|PDB:4TY0, ECO:0007744|PDB:4U03, ECO:0007744|PDB:4U0N, ECO:0007744|PDB:4XJ5"; METAL 133; /note="Magnesium; catalytic"; /evidence="ECO:0000269|PubMed:25131990, ECO:0000269|PubMed:25201413, ECO:0000269|PubMed:25865248, ECO:0007744|PDB:4TXY, ECO:0007744|PDB:4TXZ, ECO:0007744|PDB:4TY0, ECO:0007744|PDB:4U03, ECO:0007744|PDB:4U0N, ECO:0007744|PDB:4XJ5"; METAL 193; /note="Magnesium; catalytic"; /evidence="ECO:0000269|PubMed:25131990, ECO:0000269|PubMed:25201413, ECO:0000269|PubMed:25865248, ECO:0007744|PDB:4TXY, ECO:0007744|PDB:4TXZ, ECO:0007744|PDB:4TY0, ECO:0007744|PDB:4U03, ECO:0007744|PDB:4U0N, ECO:0007744|PDB:4XJ5" |
| Rhea ID | RHEA:35647; RHEA:35648 |
| Cross Reference Brenda | 2.7.7.B24; |