CGAP3_VIBCH
ID CGAP3_VIBCH Reviewed; 460 AA.
AC Q9KL18;
DT 20-JAN-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 95.
DE RecName: Full=3'3'-cGAMP-specific phosphodiesterase 3 {ECO:0000303|PubMed:25837739};
DE Short=3'3'-cGAMP PDE 3 {ECO:0000303|PubMed:25837739};
DE Short=V-cGAP3 {ECO:0000303|PubMed:25837739};
DE EC=3.1.4.- {ECO:0000269|PubMed:25837739, ECO:0000269|PubMed:30365951};
GN OrderedLocusNames=VC_A0931 {ECO:0000312|EMBL:AAF96828.1};
OS Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Vibrionales; Vibrionaceae;
OC Vibrio.
OX NCBI_TaxID=243277;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 39315 / El Tor Inaba N16961;
RX PubMed=10952301; DOI=10.1038/35020000;
RA Heidelberg J.F., Eisen J.A., Nelson W.C., Clayton R.A., Gwinn M.L.,
RA Dodson R.J., Haft D.H., Hickey E.K., Peterson J.D., Umayam L.A., Gill S.R.,
RA Nelson K.E., Read T.D., Tettelin H., Richardson D.L., Ermolaeva M.D.,
RA Vamathevan J.J., Bass S., Qin H., Dragoi I., Sellers P., McDonald L.A.,
RA Utterback T.R., Fleischmann R.D., Nierman W.C., White O., Salzberg S.L.,
RA Smith H.O., Colwell R.R., Mekalanos J.J., Venter J.C., Fraser C.M.;
RT "DNA sequence of both chromosomes of the cholera pathogen Vibrio
RT cholerae.";
RL Nature 406:477-483(2000).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, INDUCTION, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF 317-HIS-ASP-318.
RC STRAIN=ATCC 39315 / El Tor Inaba N16961;
RX PubMed=25837739; DOI=10.1038/cr.2015.40;
RA Gao J., Tao J., Liang W., Zhao M., Du X., Cui S., Duan H., Kan B., Su X.,
RA Jiang Z.;
RT "Identification and characterization of phosphodiesterases that
RT specifically degrade 3'3'-cyclic GMP-AMP.";
RL Cell Res. 25:539-550(2015).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.76 ANGSTROMS) OF 10-451 OF MUTANT ALA-440/ALA-441,
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES,
RP DOMAIN, SUBUNIT, MUTAGENESIS OF LEU-13; LEU-17; LEU-21 AND LYS-321,
RP REACTION MECHANISM, AND ACTIVE SITE.
RC STRAIN=ATCC 39315 / El Tor Inaba N16961;
RX PubMed=30365951; DOI=10.1016/j.jmb.2018.10.010;
RA Deng M.J., Tao J., Chao E., Ye Z.Y., Jiang Z., Yu J., Su X.D.;
RT "Novel Mechanism for Cyclic Dinucleotide Degradation Revealed by Structural
RT Studies of Vibrio Phosphodiesterase V-cGAP3.";
RL J. Mol. Biol. 430:5080-5093(2018).
CC -!- FUNCTION: Phosphodiesterase (PDE) that catalyzes the hydrolysis of
CC 3'3'-cyclic GMP-AMP (3'3'-cGAMP), leading to linear 5'-pApG
CC (PubMed:25837739, PubMed:30365951). Counteracts the function of the
CC 3'3'-cGAMP synthase DncV, and is involved in the modulation of
CC intracellular 3'3'-cGAMP levels. Enhances bacterial chemotaxis and
CC inhibits intestinal colonization in vivo. Thus exerts a crucial role in
CC regulating bacterial infectivity through catalyzing 3'3'-cGAMP
CC degradation. Is specific for 3'3'-cGAMP since it cannot degrade other
CC cGAMP linkage isomers (3'2'-, 2'3'-, and 2'2'-cGAMPs); is also able to
CC hydrolyze c-di-GMP but not c-di-AMP (PubMed:25837739).
CC {ECO:0000269|PubMed:25837739, ECO:0000269|PubMed:30365951}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3',3'-cGAMP + H2O = 5'-pApG-3' + H(+); Xref=Rhea:RHEA:58800,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:71501,
CC ChEBI:CHEBI:142752; Evidence={ECO:0000269|PubMed:25837739,
CC ECO:0000269|PubMed:30365951};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58801;
CC Evidence={ECO:0000305|PubMed:25837739};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:30365951};
CC Note=Requires a divalent metal cation for activity. Likely has a bi-
CC nuclear metal center. Has the highest enzyme activity with Mn(2+), and
CC when incubated with Ni(2+), its activity is about 60% lower than that
CC observed with Mn(2+). {ECO:0000269|PubMed:30365951};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 10.0. {ECO:0000269|PubMed:30365951};
CC -!- SUBUNIT: Monomer. {ECO:0000305|PubMed:30365951}.
CC -!- INDUCTION: Expression is up-regulated by 3'3'-cGAMP production (at both
CC mRNA and protein levels). {ECO:0000269|PubMed:25837739}.
CC -!- DOMAIN: Consists of two tandem domains of about 15% identity and
CC similar three-dimensional topology that interact to form a pseudo-
CC dimeric structure. The N-terminal domain (residues 1-258) plays an
CC important regulatory role in facilitating the catalytic function of the
CC C-terminal domain (residues 259-460). The N-terminal domain alone does
CC not show any activity. The C-terminal domain alone is much less active
CC comparing to the full-length protein. The full-length protein is 13
CC times more active than the C-terminal domain alone.
CC {ECO:0000269|PubMed:30365951}.
CC -!- DISRUPTION PHENOTYPE: Significant increase in the ability to colonize
CC the small intestine compared to the wild-type strain. No defect in
CC biofilm formation. Enforced DncV expression in mutant cells lacking
CC this gene causes an enhanced inhibition of chemotaxis. The double
CC mutant lacking both VC_A0681 and VC_A0931 shows enhanced bacterial
CC infectivity, and the triple one (VC_A0681, VC_A0210 and VC_A0931) has
CC the highest infectivity, which demonstrates that V-cGAPs play non-
CC redundant roles in cGAMP degradation. {ECO:0000269|PubMed:25837739}.
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DR EMBL; AE003853; AAF96828.1; -; Genomic_DNA.
DR PIR; C82399; C82399.
DR RefSeq; NP_233316.1; NC_002506.1.
DR RefSeq; WP_000109472.1; NZ_LT906615.1.
DR PDB; 5Z7C; X-ray; 2.76 A; A=10-451.
DR PDBsum; 5Z7C; -.
DR AlphaFoldDB; Q9KL18; -.
DR SMR; Q9KL18; -.
DR STRING; 243277.VC_A0931; -.
DR DNASU; 2612856; -.
DR EnsemblBacteria; AAF96828; AAF96828; VC_A0931.
DR KEGG; vch:VC_A0931; -.
DR PATRIC; fig|243277.26.peg.3544; -.
DR eggNOG; COG2206; Bacteria.
DR HOGENOM; CLU_040286_1_0_6; -.
DR OMA; FERWDGR; -.
DR BioCyc; VCHO:VCA0931-MON; -.
DR PHI-base; PHI:3233; -.
DR Proteomes; UP000000584; Chromosome 2.
DR GO; GO:0004112; F:cyclic-nucleotide phosphodiesterase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0009214; P:cyclic nucleotide catabolic process; IDA:UniProtKB.
DR CDD; cd00077; HDc; 1.
DR InterPro; IPR003607; HD/PDEase_dom.
DR InterPro; IPR006674; HD_domain.
DR InterPro; IPR037522; HD_GYP_dom.
DR SMART; SM00471; HDc; 1.
DR PROSITE; PS51831; HD; 1.
DR PROSITE; PS51832; HD_GYP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Manganese; Metal-binding; Reference proteome.
FT CHAIN 1..460
FT /note="3'3'-cGAMP-specific phosphodiesterase 3"
FT /id="PRO_0000435354"
FT DOMAIN 28..189
FT /note="HD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01175"
FT DOMAIN 260..455
FT /note="HD-GYP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01176"
FT ACT_SITE 321
FT /note="Proton donor"
FT /evidence="ECO:0000305|PubMed:30365951"
FT BINDING 317
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000305|PubMed:30365951"
FT BINDING 318
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000305|PubMed:30365951"
FT BINDING 318
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:30365951"
FT BINDING 346
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:30365951"
FT BINDING 370
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:30365951"
FT BINDING 371
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:30365951"
FT BINDING 399
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000305|PubMed:30365951"
FT MUTAGEN 13
FT /note="L->D,H: Large decrease in enzymatic activity."
FT /evidence="ECO:0000269|PubMed:30365951"
FT MUTAGEN 17
FT /note="L->H,K,T: Large decrease in enzymatic activity."
FT /evidence="ECO:0000269|PubMed:30365951"
FT MUTAGEN 21
FT /note="L->D,H: Large decrease in enzymatic activity."
FT /evidence="ECO:0000269|PubMed:30365951"
FT MUTAGEN 317..318
FT /note="HD->AA: Loss of enzymatic activity."
FT /evidence="ECO:0000269|PubMed:25837739"
FT MUTAGEN 321
FT /note="K->A,C,D,N,R,S,T,V: Almost loss of activity."
FT /evidence="ECO:0000269|PubMed:30365951"
FT HELIX 10..23
FT /evidence="ECO:0007829|PDB:5Z7C"
FT HELIX 31..44
FT /evidence="ECO:0007829|PDB:5Z7C"
FT TURN 45..47
FT /evidence="ECO:0007829|PDB:5Z7C"
FT HELIX 50..61
FT /evidence="ECO:0007829|PDB:5Z7C"
FT TURN 62..66
FT /evidence="ECO:0007829|PDB:5Z7C"
FT HELIX 96..106
FT /evidence="ECO:0007829|PDB:5Z7C"
FT HELIX 113..125
FT /evidence="ECO:0007829|PDB:5Z7C"
FT HELIX 129..148
FT /evidence="ECO:0007829|PDB:5Z7C"
FT HELIX 153..156
FT /evidence="ECO:0007829|PDB:5Z7C"
FT TURN 157..163
FT /evidence="ECO:0007829|PDB:5Z7C"
FT TURN 171..173
FT /evidence="ECO:0007829|PDB:5Z7C"
FT HELIX 177..179
FT /evidence="ECO:0007829|PDB:5Z7C"
FT HELIX 182..199
FT /evidence="ECO:0007829|PDB:5Z7C"
FT HELIX 202..212
FT /evidence="ECO:0007829|PDB:5Z7C"
FT TURN 213..215
FT /evidence="ECO:0007829|PDB:5Z7C"
FT HELIX 219..230
FT /evidence="ECO:0007829|PDB:5Z7C"
FT HELIX 234..238
FT /evidence="ECO:0007829|PDB:5Z7C"
FT HELIX 243..248
FT /evidence="ECO:0007829|PDB:5Z7C"
FT HELIX 253..256
FT /evidence="ECO:0007829|PDB:5Z7C"
FT HELIX 261..278
FT /evidence="ECO:0007829|PDB:5Z7C"
FT TURN 281..284
FT /evidence="ECO:0007829|PDB:5Z7C"
FT HELIX 285..299
FT /evidence="ECO:0007829|PDB:5Z7C"
FT HELIX 304..316
FT /evidence="ECO:0007829|PDB:5Z7C"
FT STRAND 326..328
FT /evidence="ECO:0007829|PDB:5Z7C"
FT TURN 339..345
FT /evidence="ECO:0007829|PDB:5Z7C"
FT HELIX 346..357
FT /evidence="ECO:0007829|PDB:5Z7C"
FT HELIX 362..366
FT /evidence="ECO:0007829|PDB:5Z7C"
FT HELIX 385..404
FT /evidence="ECO:0007829|PDB:5Z7C"
FT HELIX 416..425
FT /evidence="ECO:0007829|PDB:5Z7C"
FT HELIX 434..444
FT /evidence="ECO:0007829|PDB:5Z7C"
SQ SEQUENCE 460 AA; 51291 MW; E160C15151DC3D2F CRC64;
MSVAQNTFPL SELMISLTTA LDMTEGQPPE HCIRCCWIGM HIGMQLELSE PELHDLFFTL
LLKDAGCSSN AARICELYAT DDLTFKRRYK TVGTSLSSVI NFIVKNTGSE QSWTERILTT
IDILKNGNDY AQELIQTRCT RGADVARELR FSEAVAQGIH SLDEHWNGQG RPEQRKGEAI
PLFSRIALLA QVFDVFQMEH SIEEALQEIM ARSGVWFDPK LVEVVEQLVE NPRFLSGLKA
TDISQRVMNL PPAQAHLPLD DAYLECIVTA FGKIVDAKSP YTAGHSERVA VYTDLIARQL
AISDADRIWL RRAALLHDIG KLGVSNAILD KPGKLDEAEW RAVQAHAAYT EQILYKLSPF
KTLARMAGAH HEKLDGTGYP RGVNGDEISL MTRIITTADI FDALSAERPY RAAMPIDKAL
AIMEENLHTA IDPECFAALK KALNLLPDEY TQLPHSSDKT
