CDND_PSEAI
ID CDND_PSEAI Reviewed; 300 AA.
AC P0DTF7;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2021, sequence version 1.
DT 03-AUG-2022, entry version 6.
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-NTase023 {ECO:0000303|PubMed:30787435};
DE AltName: Full=Cyclic AMP-AMP-GMP synthase {ECO:0000305|PubMed:30787435};
DE EC=2.7.7.- {ECO:0000269|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=cdnD {ECO:0000303|PubMed:30787435}; ORFNames=A4W92_29535;
OS Pseudomonas aeruginosa.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pseudomonadales;
OC Pseudomonadaceae; Pseudomonas.
OX NCBI_TaxID=287;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 27853 / DSM 1117 / CIP 76.110 / JCM 6119 / LMG 6395 / NCIMB
RC 12469;
RX PubMed=27139485; DOI=10.1128/aac.00434-16;
RA Feng Y., Jonker M.J., Moustakas I., Brul S., Ter Kuile B.H.;
RT "Dynamics of Mutations during Development of Resistance by Pseudomonas
RT aeruginosa against Five Antibiotics.";
RL Antimicrob. Agents Chemother. 60:4229-4236(2016).
RN [2]
RP NOMENCLATURE, AND SIMILARITY.
RC STRAIN=ATCC 27853 / DSM 1117 / CIP 76.110 / JCM 6119 / LMG 6395 / NCIMB
RC 12469;
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:6P82, ECO:0007744|PDB:6P8J, ECO:0007744|PDB:6P8U}
RP X-RAY CRYSTALLOGRAPHY (1.47 ANGSTROMS) OF 2-300 APO-FORM AND WITH ATP AND
RP MAGNESIUM, X-RAY CRYSTALLOGRAPHY (1.89 ANGSTROMS) OF 2-300 IN COMPLEX WITH
RP CAP7 AND CLOSURE PEPTIDE, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY
RP REGULATION, SUBUNIT, DOMAIN, MUTAGENESIS OF 62-ASP--ASP-64 AND GLU-221, AND
RP ATP-BINDING.
RC STRAIN=ATCC 27853 / DSM 1117 / CIP 76.110 / JCM 6119 / LMG 6395 / NCIMB
RC 12469;
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 at pH 8.5. At pH 7.5 also makes
CC 3',3',3'-cyclic AMP-AMP-GMP. Binds ATP and much less well to GTP.
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 + GTP = cyclic AMP-AMP-GMP + 3 diphosphate;
CC Xref=Rhea:RHEA:60476, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:37565, ChEBI:CHEBI:143810;
CC 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=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:31932165};
CC Note=Crystallized with and without Mg-ATP.
CC {ECO:0000269|PubMed:31932165};
CC -!- ACTIVITY REGULATION: Activated for cAAA synthesis by Cap7 (also called
CC HORMA2) and by Cap7:Cap8 (HORMA2:HORMA3). Does not require dsDNA for
CC activity. The CdnD:Cap7:Cap8 complex (also called CdnD:HORMA2:HORMA3)
CC is deactivated by Cap6 (also called Trip13).
CC {ECO:0000269|PubMed:31932165}.
CC -!- SUBUNIT: Interacts individually with Cap7 and Cap8; forms
CC CdnD:Cap7:Cap8 complexes with stoichiometries of 1:1:1 and 2:1:1.
CC {ECO:0000269|PubMed:31932165}.
CC -!- DOMAIN: The 2 domains are closer in the ATP-bound enzyme.
CC {ECO:0000269|PubMed:31932165}.
CC -!- SIMILARITY: Belongs to the CD-NTase family. D05 subfamily.
CC {ECO:0000305|PubMed:30787435}.
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DR EMBL; CP015117; AMX91006.1; -; Genomic_DNA.
DR RefSeq; WP_003090158.1; NZ_WXZT01000006.1.
DR PDB; 6P82; X-ray; 2.05 A; A/B/C/D=2-300.
DR PDB; 6P8J; X-ray; 1.47 A; A/B/C/D=2-300.
DR PDB; 6P8U; X-ray; 1.89 A; A=2-300.
DR PDBsum; 6P82; -.
DR PDBsum; 6P8J; -.
DR PDBsum; 6P8U; -.
DR AlphaFoldDB; P0DTF7; -.
DR SMR; P0DTF7; -.
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..300
FT /note="Cyclic AMP-AMP-AMP synthase"
FT /id="PRO_0000451839"
FT BINDING 50..56
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:31932165,
FT ECO:0007744|PDB:6P8J"
FT BINDING 62
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:31932165,
FT ECO:0007744|PDB:6P8J"
FT BINDING 64
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:31932165,
FT ECO:0007744|PDB:6P8J, ECO:0007744|PDB:6P8U"
FT BINDING 130
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:31932165,
FT ECO:0007744|PDB:6P8J"
FT BINDING 154..159
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:31932165,
FT ECO:0007744|PDB:6P8J"
FT BINDING 182
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:31932165,
FT ECO:0007744|PDB:6P8J"
FT BINDING 199
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:31932165,
FT ECO:0007744|PDB:6P8J"
FT BINDING 245
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:31932165,
FT ECO:0007744|PDB:6P8J"
FT MUTAGEN 62..64
FT /note="DID->NIN: Prevents formation of second messenger,
FT binds ATP as well as wild-type."
FT /evidence="ECO:0000269|PubMed:31932165"
FT MUTAGEN 221
FT /note="E->A,K: No longer interacts with Cap7."
FT /evidence="ECO:0000269|PubMed:31932165"
FT HELIX 4..14
FT /evidence="ECO:0007829|PDB:6P8J"
FT HELIX 19..39
FT /evidence="ECO:0007829|PDB:6P8J"
FT STRAND 42..48
FT /evidence="ECO:0007829|PDB:6P8J"
FT HELIX 50..53
FT /evidence="ECO:0007829|PDB:6P8J"
FT STRAND 63..69
FT /evidence="ECO:0007829|PDB:6P8J"
FT HELIX 71..78
FT /evidence="ECO:0007829|PDB:6P8J"
FT HELIX 81..96
FT /evidence="ECO:0007829|PDB:6P8J"
FT HELIX 98..100
FT /evidence="ECO:0007829|PDB:6P8J"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:6P8J"
FT STRAND 105..111
FT /evidence="ECO:0007829|PDB:6P8J"
FT STRAND 128..136
FT /evidence="ECO:0007829|PDB:6P8J"
FT STRAND 138..145
FT /evidence="ECO:0007829|PDB:6P8J"
FT TURN 146..149
FT /evidence="ECO:0007829|PDB:6P8J"
FT STRAND 150..154
FT /evidence="ECO:0007829|PDB:6P8J"
FT HELIX 156..168
FT /evidence="ECO:0007829|PDB:6P8J"
FT TURN 169..172
FT /evidence="ECO:0007829|PDB:6P8J"
FT HELIX 174..185
FT /evidence="ECO:0007829|PDB:6P8J"
FT HELIX 188..190
FT /evidence="ECO:0007829|PDB:6P8J"
FT STRAND 195..198
FT /evidence="ECO:0007829|PDB:6P8J"
FT HELIX 200..209
FT /evidence="ECO:0007829|PDB:6P8J"
FT HELIX 218..232
FT /evidence="ECO:0007829|PDB:6P8J"
FT STRAND 242..244
FT /evidence="ECO:0007829|PDB:6P8J"
FT HELIX 247..249
FT /evidence="ECO:0007829|PDB:6P8J"
FT HELIX 253..278
FT /evidence="ECO:0007829|PDB:6P8J"
FT HELIX 282..293
FT /evidence="ECO:0007829|PDB:6P8J"
SQ SEQUENCE 300 AA; 34011 MW; 077FB9E806241B7E CRC64;
MLSIDEAFRK FKSRLELNER EQKNASQRQN EVRDYLQTKF GIARSFLTGS YARYTKTKPL
KDIDIFFVLK DSEKHYHGKA ASVVLDDFHS ALVEKYGSAA VRKQARSINV DFGVHIDAED
NTDYRVVSVD AVPAFDTGDQ YEIPDTASGK WIKTDPEIHK DKATAAHQAY ANEWKGLVRM
VKYWNNNPKH GDLKPVKPSF LIEVMALECL YGGWGGSFDR EIQSFFATLA DRVHDEWPDP
AGLGPAISND MDAARKQRAQ QLLFQASQDA SIAIDHARRG RNIEALRAWR ALFGPKFPLS
