CDNC_ECOM1
ID CDNC_ECOM1 Reviewed; 321 AA.
AC D7Y2H2;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2021, sequence version 2.
DT 03-AUG-2022, entry version 37.
DE RecName: Full=Cyclic AMP-AMP-AMP synthase {ECO:0000303|PubMed:31932165};
DE EC=2.7.7.- {ECO:0000305|PubMed:31932165};
DE AltName: Full=CD-NTase018 {ECO:0000303|PubMed:30787435};
DE AltName: Full=c-di-AMP synthase {ECO:0000305|PubMed:31932165};
DE EC=2.7.7.85 {ECO:0000269|PubMed:31932165};
GN Name=cdnC {ECO:0000303|PubMed:30787435};
GN ORFNames=HMPREF9540_01758 {ECO:0000312|EMBL:EFJ98156.1};
OS Escherichia coli (strain MS 115-1).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=749537;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MS 115-1;
RA Weinstock G., Sodergren E., Clifton S., Fulton L., Fulton B., Courtney L.,
RA Fronick C., Harrison M., Strong C., Farmer C., Delahaunty K., Markovic C.,
RA Hall O., Minx P., Tomlinson C., Mitreva M., Hou S., Chen J., Wollam A.,
RA Pepin K.H., Johnson M., Bhonagiri V., Zhang X., Suruliraj S., Warren W.,
RA Chinwalla A., Mardis E.R., Wilson R.K.;
RL Submitted (MAY-2010) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NOMENCLATURE, AND SIMILARITY.
RC STRAIN=MS 115-1;
RX PubMed=30787435; DOI=10.1038/s41586-019-0953-5;
RA Whiteley A.T., Eaglesham J.B., de Oliveira Mann C.C., Morehouse B.R.,
RA Lowey B., Nieminen E.A., Danilchanka O., King D.S., Lee A.S.Y.,
RA Mekalanos J.J., Kranzusch P.J.;
RT "Bacterial cGAS-like enzymes synthesize diverse nucleotide signals.";
RL Nature 567:194-199(2019).
RN [3]
RP CLASSIFICATION AND NOMENCLATURE.
RX PubMed=32839535; DOI=10.1038/s41564-020-0777-y;
RA Millman A., Melamed S., Amitai G., Sorek R.;
RT "Diversity and classification of cyclic-oligonucleotide-based anti-phage
RT signalling systems.";
RL Nat. Microbiol. 5:1608-1615(2020).
RN [4] {ECO:0007744|PDB:6P80, ECO:0007744|PDB:6P8V, ECO:0007744|PDB:6U7B}
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 4-321 IN COMPLEX WITH ATP AND
RP MAGNESIUM, X-RAY CRYSTALLOGRAPHY (2.09 ANGSTROMS) OF 2-321 IN COMPLEX WITH
RP CAP7 AND WITH CLOSURE PEPTIDE, X-RAY CRYSTALLOGRAPHY (2.64 ANGSTROMS) OF
RP 2-321 IN COMPLEX WITH CAP6 AND CAP7, FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, ACTIVITY REGULATION, INTERACTION WITH CAP7, DOMAIN, MUTAGENESIS
RP OF 23-LYS--LYS-34; ARG-30; ARG-54; 72-ASP--ASP-74 AND LYS-170, AND
RP ATP-BINDING.
RC STRAIN=MS 115-1;
RX PubMed=31932165; DOI=10.1016/j.molcel.2019.12.009;
RA Ye Q., Lau R.K., Mathews I.T., Birkholz E.A., Watrous J.D., Azimi C.S.,
RA Pogliano J., Jain M., Corbett K.D.;
RT "HORMA Domain Proteins and a Trip13-like ATPase Regulate Bacterial cGAS-
RT like Enzymes to Mediate Bacteriophage Immunity.";
RL Mol. Cell 77:709-722(2020).
CC -!- FUNCTION: CBASS (cyclic oligonucleotide-based antiphage signaling
CC system) provides immunity against bacteriophage. The CD-NTase protein
CC synthesizes cyclic nucleotides in response to infection; these serve as
CC specific second messenger signals. The signals activate a diverse range
CC of effectors, leading to bacterial cell death and thus abortive phage
CC infection. A type III-C(AAA) CBASS system (PubMed:32839535).
CC {ECO:0000269|PubMed:31932165, ECO:0000303|PubMed:32839535}.
CC -!- FUNCTION: Cyclic nucleotide synthase that upon activation catalyzes the
CC synthesis of 2',3',3'-cyclic AMP-AMP-AMP (cAAA) as the major product,
CC and c-di-AMP as a minor product. Binds ATP or AMP depending on its
CC partner protein, and probably catalytic cycle.
CC {ECO:0000269|PubMed:31932165}.
CC -!- FUNCTION: Protects E.coli strain JP313 against bacteriophage lambda
CC cI- infection. When the cdnC-cap7-cap6-nucC operon is transformed into
CC a susceptible strain it confers bacteriophage immunity. Mutations in
CC the sensor (Cap7 also called HORMA) or effector proteins (CdnC, NucC)
CC but not the disassembly protein (Cap6 also called Trip13) no longer
CC confer immunity. The presence of the intact operon leads to culture
CC collapse and cell death, which occurs before the phage has finished its
CC replication cycle, thus protecting non-infected bacteria by aborting
CC the phage infection and preventing its propagation.
CC {ECO:0000269|PubMed:31932165}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3 ATP = 2',3',3'-c-tri-AMP + 3 diphosphate;
CC Xref=Rhea:RHEA:65488, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:156512; Evidence={ECO:0000269|PubMed:31932165};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 ATP = 3',3'-c-di-AMP + 2 diphosphate; Xref=Rhea:RHEA:35655,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:71500; EC=2.7.7.85;
CC Evidence={ECO:0000269|PubMed:31932165};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:31932165};
CC -!- ACTIVITY REGULATION: The 2:2 CdnC:Cap7 (Cap7 is also called HORMA)
CC complex is activated for cAAA synthesis by long dsDNA, but not 40 bp
CC dsDNA or ssDNA; the 1:1 complex is inactive in vitro. The 2:2:DNA
CC complex is deactivated by Cap6 (also called Trip13).
CC {ECO:0000269|PubMed:31932165}.
CC -!- SUBUNIT: Forms complexes with Cap7 with 1:1 and 2:2 stoichimetry, and a
CC 1:1:6 CdnC:Cap7:Cap6 complex. {ECO:0000269|PubMed:31932165}.
CC -!- DOMAIN: In the disassembly complex (PDB:6P8V) Cap6 (also called Trip13)
CC crystallizes as a right-handed spiral; the top 4 subunits bind ATP
CC while the bottom 2 do not. A CdnC monomer lies along the surface of the
CC hexamer at the interface of subunits 5 and 6, with Cap7 (also called
CC HORMA) at its tip, over the central hexamer pore. The N-terminus of
CC Cap7 extends into the pore, contacting 5/6 Cap6 subunits.
CC {ECO:0000269|PubMed:31932165}.
CC -!- SIMILARITY: Belongs to the CD-NTase family. A01 subfamily.
CC {ECO:0000305|PubMed:30787435}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EFJ98156.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305|PubMed:31932165};
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DR EMBL; ADTL01000141; EFJ98156.1; ALT_INIT; Genomic_DNA.
DR RefSeq; WP_000102473.1; NZ_GG771785.1.
DR PDB; 6P80; X-ray; 1.50 A; A=4-321.
DR PDB; 6P8V; X-ray; 2.64 A; G=2-321.
DR PDB; 6U7B; X-ray; 2.09 A; A/C=2-321.
DR PDBsum; 6P80; -.
DR PDBsum; 6P8V; -.
DR PDBsum; 6U7B; -.
DR AlphaFoldDB; D7Y2H2; -.
DR SMR; D7Y2H2; -.
DR EnsemblBacteria; EFJ98156; EFJ98156; HMPREF9540_01758.
DR HOGENOM; CLU_073286_0_0_6; -.
DR Proteomes; UP000032708; Unassembled WGS sequence.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0106408; F:diadenylate cyclase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0009117; P:nucleotide metabolic process; IEA:UniProtKB-KW.
DR CDD; cd05400; NT_2-5OAS_ClassI-CCAase; 1.
DR Gene3D; 3.30.460.10; -; 1.
DR InterPro; IPR006116; NT_2-5OAS_ClassI-CCAase.
DR InterPro; IPR043519; NT_sf.
DR SUPFAM; SSF81301; SSF81301; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antiviral defense; ATP-binding; Magnesium; Metal-binding;
KW Nucleotide metabolism; Nucleotide-binding; Nucleotidyltransferase;
KW Transferase.
FT CHAIN 1..321
FT /note="Cyclic AMP-AMP-AMP synthase"
FT /id="PRO_0000451838"
FT BINDING 63
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000269|PubMed:31932165,
FT ECO:0007744|PDB:6U7B"
FT BINDING 63
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:31932165,
FT ECO:0007744|PDB:6P80, ECO:0007744|PDB:6P8V"
FT BINDING 72
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:31932165,
FT ECO:0007744|PDB:6U7B"
FT BINDING 74
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:31932165,
FT ECO:0007744|PDB:6P80, ECO:0007744|PDB:6P8V"
FT BINDING 74
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:31932165,
FT ECO:0007744|PDB:6P80, ECO:0007744|PDB:6P8V,
FT ECO:0007744|PDB:6U7B"
FT BINDING 162
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000269|PubMed:31932165,
FT ECO:0007744|PDB:6U7B"
FT BINDING 162
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:31932165,
FT ECO:0007744|PDB:6P80, ECO:0007744|PDB:6P8V"
FT BINDING 201..203
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:31932165,
FT ECO:0007744|PDB:6P80, ECO:0007744|PDB:6P8V"
FT BINDING 203
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000269|PubMed:31932165,
FT ECO:0007744|PDB:6U7B"
FT BINDING 270
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000269|PubMed:31932165,
FT ECO:0007744|PDB:6U7B"
FT BINDING 270
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:31932165,
FT ECO:0007744|PDB:6P80"
FT MUTAGEN 23..34
FT /note="KVKADDFREQAK->AVKADDFAEQAA: Prevents formation of
FT second messenger, no longer binds DNA."
FT /evidence="ECO:0000269|PubMed:31932165"
FT MUTAGEN 30
FT /note="R->A: Prevents formation of second messenger,
FT decreased DNA-binding."
FT /evidence="ECO:0000269|PubMed:31932165"
FT MUTAGEN 54
FT /note="R->A: Prevents formation of second messenger."
FT /evidence="ECO:0000269|PubMed:31932165"
FT MUTAGEN 72..74
FT /note="DID->NIN: Prevents formation of second messenger. No
FT longer confers phage immunity."
FT /evidence="ECO:0000269|PubMed:31932165"
FT MUTAGEN 170
FT /note="K->A: Prevents formation of second messenger."
FT /evidence="ECO:0000269|PubMed:31932165"
FT TURN 3..5
FT /evidence="ECO:0007829|PDB:6U7B"
FT HELIX 8..18
FT /evidence="ECO:0007829|PDB:6P80"
FT HELIX 23..46
FT /evidence="ECO:0007829|PDB:6P80"
FT STRAND 51..57
FT /evidence="ECO:0007829|PDB:6P80"
FT HELIX 60..63
FT /evidence="ECO:0007829|PDB:6P80"
FT STRAND 72..79
FT /evidence="ECO:0007829|PDB:6P80"
FT STRAND 81..84
FT /evidence="ECO:0007829|PDB:6U7B"
FT HELIX 88..102
FT /evidence="ECO:0007829|PDB:6P80"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:6P8V"
FT HELIX 108..110
FT /evidence="ECO:0007829|PDB:6P80"
FT STRAND 111..113
FT /evidence="ECO:0007829|PDB:6P80"
FT STRAND 115..120
FT /evidence="ECO:0007829|PDB:6P80"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:6P8V"
FT STRAND 128..135
FT /evidence="ECO:0007829|PDB:6P80"
FT HELIX 140..142
FT /evidence="ECO:0007829|PDB:6P80"
FT STRAND 144..147
FT /evidence="ECO:0007829|PDB:6P80"
FT TURN 149..151
FT /evidence="ECO:0007829|PDB:6P80"
FT STRAND 154..157
FT /evidence="ECO:0007829|PDB:6P80"
FT HELIX 159..172
FT /evidence="ECO:0007829|PDB:6P80"
FT HELIX 176..194
FT /evidence="ECO:0007829|PDB:6P80"
FT HELIX 202..214
FT /evidence="ECO:0007829|PDB:6P80"
FT HELIX 222..236
FT /evidence="ECO:0007829|PDB:6P80"
FT STRAND 246..248
FT /evidence="ECO:0007829|PDB:6P80"
FT HELIX 250..252
FT /evidence="ECO:0007829|PDB:6P80"
FT TURN 272..275
FT /evidence="ECO:0007829|PDB:6P80"
FT HELIX 278..300
FT /evidence="ECO:0007829|PDB:6P80"
FT HELIX 304..315
FT /evidence="ECO:0007829|PDB:6P80"
SQ SEQUENCE 321 AA; 36172 MW; 92A5B4308514DA3D CRC64;
MSTEHVDHKT IARFAEDKVN LPKVKADDFR EQAKRLQNKL EGYLSDHPDF SLKRMIPSGS
LAKGTALRSL NDIDVAVYIS GSDAPQDLRG LLDYLADRLR KAFPNFSPDQ VKPQTYSVTV
SFRGSGLDVD IVPVLYSGLP DWRGHLISQE DGSFLETSIP LHLDFIKARK RAAPKHFAQV
VRLAKYWARL MKQERPNFRF KSFMIELILA KLLDNGVDFS NYPEALQAFF SYLVSTELRE
RIVFEDNYPA SKIGTLSDLV QIIDPVNPVN NVARLYTQSN VDAIIDAAMD AGDAIDAAFY
APTKQLTVTY WQKVFGSSFQ G
