CDPD2_PSEAE
ID CDPD2_PSEAE Reviewed; 393 AA.
AC Q9HV27;
DT 05-JUL-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Cyclic di-GMP phosphodiesterase PA4781 {ECO:0000303|PubMed:19170727};
DE EC=3.1.4.- {ECO:0000269|PubMed:24066157};
GN OrderedLocusNames=PA4781 {ECO:0000312|EMBL:AAG08167.1};
OS Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM
OS 14847 / LMG 12228 / 1C / PRS 101 / PAO1).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pseudomonadales;
OC Pseudomonadaceae; Pseudomonas.
OX NCBI_TaxID=208964;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=10984043; DOI=10.1038/35023079;
RA Stover C.K., Pham X.-Q.T., Erwin A.L., Mizoguchi S.D., Warrener P.,
RA Hickey M.J., Brinkman F.S.L., Hufnagle W.O., Kowalik D.J., Lagrou M.,
RA Garber R.L., Goltry L., Tolentino E., Westbrock-Wadman S., Yuan Y.,
RA Brody L.L., Coulter S.N., Folger K.R., Kas A., Larbig K., Lim R.M.,
RA Smith K.A., Spencer D.H., Wong G.K.-S., Wu Z., Paulsen I.T., Reizer J.,
RA Saier M.H. Jr., Hancock R.E.W., Lory S., Olson M.V.;
RT "Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic
RT pathogen.";
RL Nature 406:959-964(2000).
RN [2]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=19170727; DOI=10.1111/j.1462-2920.2008.01842.x;
RA Ryan R.P., Lucey J., O'Donovan K., McCarthy Y., Yang L., Tolker-Nielsen T.,
RA Dow J.M.;
RT "HD-GYP domain proteins regulate biofilm formation and virulence in
RT Pseudomonas aeruginosa.";
RL Environ. Microbiol. 11:1126-1136(2009).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBUNIT, PHOSPHORYLATION, AND MUTAGENESIS OF GLU-314.
RX PubMed=24066157; DOI=10.1371/journal.pone.0074920;
RA Stelitano V., Giardina G., Paiardini A., Castiglione N., Cutruzzola F.,
RA Rinaldo S.;
RT "C-di-GMP hydrolysis by Pseudomonas aeruginosa HD-GYP phosphodiesterases:
RT analysis of the reaction mechanism and novel roles for pGpG.";
RL PLoS ONE 8:E74920-E74920(2013).
RN [4] {ECO:0007744|PDB:4R8Z}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 151-368 IN COMPLEX WITH NICKEL,
RP SUBUNIT, AND DOMAIN.
RX PubMed=25691523; DOI=10.1128/jb.02606-14;
RA Rinaldo S., Paiardini A., Stelitano V., Brunotti P., Cervoni L.,
RA Fernicola S., Protano C., Vitali M., Cutruzzola F., Giardina G.;
RT "Structural basis of functional diversification of the HD-GYP domain
RT revealed by the Pseudomonas aeruginosa PA4781 protein, which displays an
RT unselective bimetallic binding site.";
RL J. Bacteriol. 197:1525-1535(2015).
CC -!- FUNCTION: Phosphodiesterase (PDE) that catalyzes the hydrolysis of
CC cyclic diguanylate (c-di-GMP) to GMP (PubMed:19170727,
CC PubMed:24066157). Hydrolyzes c-di-GMP to GMP in a two-step reaction,
CC via the linear intermediate 5'-phosphoguanylyl(3'->5')guanosine (pGpG).
CC In vitro, can use pGpG as an alternative substrate and hydrolyze it
CC into GMP (PubMed:24066157). Acts in regulation of motility, synthesis
CC of virulence determinants and biofilm architecture (PubMed:19170727).
CC May act preferentially as a pGpG binding protein (PubMed:24066157).
CC {ECO:0000269|PubMed:19170727, ECO:0000269|PubMed:24066157}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cyclic di-3',5'-guanylate + 2 H2O = 2 GMP + 2 H(+);
CC Xref=Rhea:RHEA:52928, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:58115, ChEBI:CHEBI:58805;
CC Evidence={ECO:0000269|PubMed:24066157};
CC -!- ACTIVITY REGULATION: Phosphodiesterase activity is activated by
CC phosphorylation of the N-terminal regulatory domain. Phosphorylation
CC triggers a conformational change of the HD-GYP domain, which renders
CC the active site accessible. {ECO:0000269|PubMed:24066157}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=119 uM for c-di-GMP {ECO:0000269|PubMed:24066157};
CC KM=27 uM for pGpG {ECO:0000269|PubMed:24066157};
CC Note=kcat is 0.0002 sec(-1). {ECO:0000269|PubMed:24066157};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:24066157,
CC ECO:0000269|PubMed:25691523}.
CC -!- DOMAIN: Contains an unselective bimetallic binding site, with a high-
CC affinity site (H-site) and a low-affinity site (L-site). Metal binding
CC to the H-site triggers the binding to the L-site. This bimetallic
CC center may play a structural more than a catalytic role.
CC {ECO:0000269|PubMed:25691523}.
CC -!- PTM: Phosphorylated. {ECO:0000269|PubMed:24066157}.
CC -!- DISRUPTION PHENOTYPE: Disruption mutant has increased levels of cyclic
CC di-GMP. Mutation leads to reduction in both swarming and twitching
CC motility, to an increase in pyoverdine production, and a reduction in
CC virulence. It produces a biofilm with little heterogeneity.
CC {ECO:0000269|PubMed:19170727}.
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DR EMBL; AE004091; AAG08167.1; -; Genomic_DNA.
DR PIR; C83049; C83049.
DR RefSeq; NP_253469.1; NC_002516.2.
DR RefSeq; WP_003102241.1; NZ_QZGE01000018.1.
DR PDB; 4R8Z; X-ray; 2.20 A; A/B=151-368.
DR PDBsum; 4R8Z; -.
DR AlphaFoldDB; Q9HV27; -.
DR SMR; Q9HV27; -.
DR STRING; 287.DR97_2126; -.
DR PaxDb; Q9HV27; -.
DR PRIDE; Q9HV27; -.
DR EnsemblBacteria; AAG08167; AAG08167; PA4781.
DR GeneID; 880075; -.
DR KEGG; pae:PA4781; -.
DR PATRIC; fig|208964.12.peg.5009; -.
DR PseudoCAP; PA4781; -.
DR HOGENOM; CLU_000445_92_10_6; -.
DR InParanoid; Q9HV27; -.
DR OMA; SHYGRIL; -.
DR PhylomeDB; Q9HV27; -.
DR BioCyc; PAER208964:G1FZ6-4894-MON; -.
DR BRENDA; 3.1.4.52; 5087.
DR Proteomes; UP000002438; Chromosome.
DR GO; GO:0071111; F:cyclic-guanylate-specific phosphodiesterase activity; IDA:PseudoCAP.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000160; P:phosphorelay signal transduction system; IEA:InterPro.
DR GO; GO:2000147; P:positive regulation of cell motility; IMP:PseudoCAP.
DR GO; GO:1900231; P:regulation of single-species biofilm formation on inanimate substrate; IMP:PseudoCAP.
DR CDD; cd00077; HDc; 1.
DR InterPro; IPR011006; CheY-like_superfamily.
DR InterPro; IPR003607; HD/PDEase_dom.
DR InterPro; IPR037522; HD_GYP_dom.
DR InterPro; IPR001789; Sig_transdc_resp-reg_receiver.
DR Pfam; PF00072; Response_reg; 1.
DR SMART; SM00471; HDc; 1.
DR SMART; SM00448; REC; 1.
DR SUPFAM; SSF52172; SSF52172; 1.
DR PROSITE; PS51832; HD_GYP; 1.
DR PROSITE; PS50110; RESPONSE_REGULATORY; 1.
PE 1: Evidence at protein level;
KW 3D-structure; c-di-GMP; Hydrolase; Metal-binding; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..393
FT /note="Cyclic di-GMP phosphodiesterase PA4781"
FT /id="PRO_0000440637"
FT DOMAIN 12..128
FT /note="Response regulatory"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00169"
FT DOMAIN 155..366
FT /note="HD-GYP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01176"
FT BINDING 180
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:25691523"
FT BINDING 220
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:25691523"
FT BINDING 221
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:25691523"
FT BINDING 221
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:25691523"
FT BINDING 249
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:25691523"
FT BINDING 281
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:25691523"
FT BINDING 282
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:25691523"
FT MOD_RES 61
FT /note="4-aspartylphosphate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00169"
FT MUTAGEN 314
FT /note="E->A: Increases affinity for c-di-GMP."
FT /evidence="ECO:0000269|PubMed:24066157"
FT HELIX 153..169
FT /evidence="ECO:0007829|PDB:4R8Z"
FT TURN 170..174
FT /evidence="ECO:0007829|PDB:4R8Z"
FT HELIX 180..196
FT /evidence="ECO:0007829|PDB:4R8Z"
FT HELIX 199..202
FT /evidence="ECO:0007829|PDB:4R8Z"
FT HELIX 207..216
FT /evidence="ECO:0007829|PDB:4R8Z"
FT HELIX 217..219
FT /evidence="ECO:0007829|PDB:4R8Z"
FT HELIX 222..226
FT /evidence="ECO:0007829|PDB:4R8Z"
FT HELIX 229..232
FT /evidence="ECO:0007829|PDB:4R8Z"
FT HELIX 240..247
FT /evidence="ECO:0007829|PDB:4R8Z"
FT HELIX 249..261
FT /evidence="ECO:0007829|PDB:4R8Z"
FT HELIX 269..280
FT /evidence="ECO:0007829|PDB:4R8Z"
FT STRAND 289..292
FT /evidence="ECO:0007829|PDB:4R8Z"
FT HELIX 296..298
FT /evidence="ECO:0007829|PDB:4R8Z"
FT HELIX 301..315
FT /evidence="ECO:0007829|PDB:4R8Z"
FT HELIX 327..335
FT /evidence="ECO:0007829|PDB:4R8Z"
FT TURN 339..341
FT /evidence="ECO:0007829|PDB:4R8Z"
FT HELIX 344..363
FT /evidence="ECO:0007829|PDB:4R8Z"
SQ SEQUENCE 393 AA; 43629 MW; D2CD7F712E8F797E CRC64;
MESMLDRPEQ ELVLVVDDTP DNLLLMRELL EEQYRVRTAG SGPAGLRAAV EEPRPDLILL
DVNMPGMDGY EVCRRLKADP LTRDIPLMFL TARADRDDEQ QGLALGAVDY LGKPVSPPIV
LARVRTHLQL KANADFLRDK SEYLELEVRR RTRQLQQLQD AVIEALATLG DLRDNPRSRH
LPRIERYVRL LAEHLAAQRA FADELTPEAV DLLSKSALLH DIGKVAVPDR VLLNPGQLDA
ADTALLQGHT RAGRDALASA ERRLGQPSGF LRFARQIAYS HHERWDGRGF PEGLAGERIP
LAARIVALAD RYDELTSRHA YRPPLAHAEA VLLIQAGAGS EFDPRLVEAF VAVADAFAEV
ARRYADSAEA LDVEMQRLEQ AVAESIELTA PPA
