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Information on EC 3.1.4.59 - cyclic-di-AMP phosphodiesterase
for references in articles please use BRENDA:EC3.1.4.59
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EC Tree 3 Hydrolases
3.1 Acting on ester bonds
3.1.4 Phosphoric-diester hydrolases
3.1.4.59 cyclic-di-AMP phosphodiesterase
IUBMB Comments
The enzyme, described from Gram-positive bacteria, degrades the second messenger cyclic di-3′,5′-adenylate. It is a membrane-bound protein that contains a cytoplasmic facing Per-Arnt-Sim (PAS) domain, a modified GGDEF domain, and a DHH/DHHA1 domain, which confers the phosphodiesterase activity. Activity requires Mn2+ and is inhibited by pApA.
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Reaction Schemes
showSynonyms
lmo0052, llmg_1816, msmeg_2630, spd_1153, spd_2032, bb0619, cyclic-di-amp phosphodiesterase, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
BB0619
CnpB
Dhhp
gdpP
GdpP protein
llmg_1816
Lmo0052
MSMEG_2630
NrnA
PDE
PDE2
PdeA
PgpH
Rv2837c
SAOUHSC_00015
SntA
SSU98_2160
YybT
gdpP
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cyclic di-3',5'-adenylate + H2O = 5'-O-phosphonoadenylyl-(3'->5')-adenosine
-
-
-
-
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SYSTEMATIC NAME
IUBMB Comments
cyclic bis(3'->5')diadenylate 3'-adenylylhydrolase
The enzyme, described from Gram-positive bacteria, degrades the second messenger cyclic di-3',5'-adenylate. It is a membrane-bound protein that contains a cytoplasmic facing Per-Arnt-Sim (PAS) domain, a modified GGDEF domain, and a DHH/DHHA1 domain, which confers the phosphodiesterase activity. Activity requires Mn2+ and is inhibited by pApA.
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
5'-O-phosphonoadenylyl-(3'->5')-adenosine + H2O
2 AMP
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?
cyclic di-3',5'-adenylate + H2O
5'-O-phosphonoadenylyl-(3'->5')-adenosine
Substrates: -
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?
cyclic di-3',5'-adenylate + H2O
5'-O-phosphonoadenylyl-(3'->5')-adenosine
Substrates: -
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?
cyclic di-3',5'-adenylate + H2O
5'-O-phosphonoadenylyl-(3'->5')-adenosine
Substrates: -
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?
cyclic di-3',5'-adenylate + H2O
5'-O-phosphonoadenylyl-(3'->5')-adenosine
Substrates: -
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?
cyclic di-3',5'-adenylate + H2O
5'-O-phosphonoadenylyl-(3'->5')-adenosine
Substrates: -
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?
cyclic di-3',5'-adenylate + H2O
5'-O-phosphonoadenylyl-(3'->5')-adenosine
Substrates: -
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?
cyclic di-3',5'-adenylate + H2O
5'-O-phosphonoadenylyl-(3'->5')-adenosine
Substrates: -
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?
cyclic di-3',5'-adenylate + H2O
5'-O-phosphonoadenylyl-(3'->5')-adenosine
Substrates: -
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?
cyclic di-3',5'-adenylate + H2O
5'-O-phosphonoadenylyl-(3'->5')-adenosine
Substrates: -
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?
cyclic di-3',5'-adenylate + H2O
5'-O-phosphonoadenylyl-(3'->5')-adenosine
Substrates: -
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?
cyclic di-3',5'-adenylate + H2O
5'-O-phosphonoadenylyl-(3'->5')-adenosine
Substrates: -
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?
cyclic di-3',5'-adenylate + H2O
5'-O-phosphonoadenylyl-(3'->5')-adenosine
-
Substrates: -
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?
cyclic di-3',5'-adenylate + H2O
5'-O-phosphonoadenylyl-(3'->5')-adenosine
Substrates: -
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?
cyclic di-3',5'-adenylate + H2O
5'-O-phosphonoadenylyl-(3'->5')-adenosine
-
Substrates: -
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?
cyclic di-3',5'-adenylate + H2O
5'-O-phosphonoadenylyl-(3'->5')-adenosine
Substrates: -
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?
cyclic di-3',5'-adenylate + H2O
5'-O-phosphonoadenylyl-(3'->5')-adenosine
Substrates: -
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?
cyclic di-3',5'-adenylate + H2O
5'-O-phosphonoadenylyl-(3'->5')-adenosine
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?
cyclic di-3',5'-adenylate + H2O
5'-O-phosphonoadenylyl-(3'->5')-adenosine
Streptococcus suis CCUG 7984
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cyclic di-3',5'-guanylate + H2O
5'-phosphoguanylyl-(3'->5')guanosine
Substrates: -
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?
cyclic di-3',5'-guanylate + H2O
5'-phosphoguanylyl-(3'->5')guanosine
Substrates: -
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?
cyclic di-3',5'-guanylate + H2O
5'-phosphoguanylyl-(3'->5')guanosine
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?
cyclic di-3',5'-guanylate + H2O
5'-phosphoguanylyl-(3'->5')guanosine
Substrates: -
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additional information
?
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Substrates: enzyme has c-di-AMP specific phosphodiesterase activity. It hydrolyzes c-di-AMP to 5'-AMP in two steps. First, it linearizes c-di-AMP into pApA , reaction of EC 3.1.4.59, which is further hydrolyzed to 5'-AMP, reaction of EC 3.1.4.60
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additional information
?
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Substrates: enzyme has c-di-AMP specific phosphodiesterase activity. It hydrolyzes c-di-AMP to 5'-AMP in two steps. First, it linearizes c-di-AMP into pApA , reaction of EC 3.1.4.59, which is further hydrolyzed to 5'-AMP, reaction of EC 3.1.4.60
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additional information
?
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Substrates: Pde is capable of converting c-di-AMP to pApA, i.e. 5'-O-phosphonoadenylyl-(3'->5')-adenosine and AMP, and hydrolyzing pApA to AMP
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additional information
?
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Substrates: Pde is capable of converting c-di-AMP to pApA, i.e. 5'-O-phosphonoadenylyl-(3'->5')-adenosine and AMP, and hydrolyzing pApA to AMP
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additional information
?
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Substrates: isoform Pde2 is capable of hydrolyzing c-di-AMP and Pde2 preferentially converts linear 5'-phosphonoadenylyl-adenosine (pApA) to AMP, reaction of EC 3.1.3.7. No substrate: ATP
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additional information
?
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Substrates: enzyme does not hydrolyze product 5'-O-phosphonoadenylyl-(3'->5')-adenosine
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additional information
?
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Substrates: isoform Pde2 is capable of hydrolyzing c-di-AMP and Pde2 preferentially converts linear 5'-phosphonoadenylyl-adenosine (pApA) to AMP, reaction of EC 3.1.3.7. No substrate: ATP
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?
additional information
?
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Substrates: Pde2 directly hydrolyzes c-di-AMP into AMP. Additionally, Pde2 degrades 5'-O-phosphonoadenylyl-(3'->5')-adenosine into AMP. Pde2 prefers substrate 5'-O-phosphonoadenylyl-(3'->5')-adenosine
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?
additional information
?
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Substrates: Pde2 directly hydrolyzes c-di-AMP into AMP. Additionally, Pde2 degrades 5'-O-phosphonoadenylyl-(3'->5')-adenosine into AMP. Pde2 prefers substrate 5'-O-phosphonoadenylyl-(3'->5')-adenosine
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?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
cyclic di-3',5'-adenylate + H2O
5'-O-phosphonoadenylyl-(3'->5')-adenosine
Substrates: -
Products: -
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?
cyclic di-3',5'-adenylate + H2O
5'-O-phosphonoadenylyl-(3'->5')-adenosine
Substrates: -
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?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
Fe2+
Pde is strictly dependent on Co2+, Mn2+, Mg2+ or Fe2+, with maximum activity with Mn2+ as a cofactor
Mg2+
Mn2+
Co2+
Pde is strictly dependent on Co2+, Mn2+, Mg2+ or Fe2+, with maximum activity with Mn2+ as a cofactor
Mg2+
Pde is strictly dependent on Co2+, Mn2+, Mg2+ or Fe2+, with maximum activity with Mn2+ as a cofactor
Mn2+
enzyme is strictly dependent on divalent cation, best cofactor is Mn2+
Mn2+
Pde is strictly dependent on Co2+, Mn2+, Mg2+ or Fe2+, with maximum activity with Mn2+ as a cofactor
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5'-O-phosphonoadenylyl-(3'->5')-adenosine
product inhibition, competitive
Clemastine
-
the histamine receptor H1 (HRH1) antagonist might exert its inhibitory effects against the biofilm formation and hemolysis in Staphylococcus aureus through targeting GdpP protein
guanosine pentaphosphate
ppGpp is a strong competitive inhibitor of the DHH/DHHA1 domain
guanosine pentaphosphate
-
c-di-AMP phosphodiesterase GdpP is inhibited in a dose-dependent manner by ppGpp
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Hypersensitivity
High temperature growth induced spontaneous mutation of llmg_1816 (gdpP) results in heat resistance and salt hypersensitivity in Lactococcus lactis.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0167
5'-O-phosphonoadenylyl-(3'->5')-adenosine
pH 7.5, 37°C
0.0364
5'-O-phosphonoadenylyl-(3'->5')-adenosine
pH 7.5, 37°C
0.0013
cyclic di-3',5'-adenylate
pH 8.3, temperature not specified in the publication
0.145
cyclic di-3',5'-adenylate
pH 8.0, 37°C, presence of 0.02 mM 5'-O-phosphonoadenylyl-(3'->5')-adenosine
0.349
cyclic di-3',5'-guanylate
pH 8.3, temperature not specified in the publication
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.55
cyclic di-3',5'-adenylate
pH 8.3, temperature not specified in the publication
0.23
cyclic di-3',5'-guanylate
pH 8.3, temperature not specified in the publication
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0359
guanosine pentaphosphate
pH 8.3, temperature not specified in the publication
0.1297
guanosine pentaphosphate
-
pH 8.5, temperature not specified in the publication
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
8.5
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
bifunctional oligoribonuclease and PAP phosphatase, cf. EC 3.1.3.7. Enzyme has a DHH/DHHA1 domain
UniProt
brenda
protein is a DHHA1 domain protein, COG3387 family member
UniProt
brenda
protein is a DHHA1 domain protein, COG3387 family member
UniProt
brenda
bifunctional oligoribonuclease and PAP phosphatase, cf. EC 3.1.3.7. Enzyme has a DHH/DHHA1 domain
UniProt
brenda
protein contains a DHH-DHHAI domain
UniProt
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
protein possesses two transmembrane helices
brenda
Highest Expressing Human Cell Lines
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug target
physiological function
additional information
drug target
CnpB interferes with host innate and adaptive immune responses and confers protection against Mycobacterium tuberculosis respiratory infection, which should be considered in vaccine development as well as a drug target
drug target
-
CnpB interferes with host innate and adaptive immune responses and confers protection against Mycobacterium tuberculosis respiratory infection, which should be considered in vaccine development as well as a drug target
-
physiological function
a Pde2 mutant strain displays a growth defect in the early growth phase. Mutation leads to an increase in cellular c-di-AMP and 5'-O-phosphonoadenylyl-(3'->5')-adenosine levels and increased resistance to oxacillin
physiological function
-
deletion of the GdpP gene impairs the processing of cysteine protease SpeB, decreases sensitivity to the antibiotic ampicillin, and attenuates virulence in a murine model of subcutaneous infection
physiological function
-
mutations within the GdpP gene, allow both laboratory and clinical isolates of Staphylococcus aureus to grow without lipoteichoic acid. Intracellular c-di-AMP levels increase drastically in GdpP deletion strains and in an lipoteichoic acid-deficient suppressor strain. An increased amount of cross-linked peptidoglycan is observed in the GdpP mutant strain. GdpP mutant strains display a 13-22% reduction in the cell size due to increased c-di-AMP levels
physiological function
deletion of either isoform Pde1 or Pde2 results in a moderate increase of the c-di-AMP levels compared with the parental strain. Deletion of both genes results in an up to 4fold increase in c-di-AMP levels compared to that of the parental strain. Both Pde1 and Pde2 play a role in pneumococcal growth. Deletion of either isoform Pde1 or Pde2 reduces the growth rate slightly, and the double mutant synergizes the reduction
physiological function
both phosphodiesterases, GdpP and PgpH, contribute to the degradation of cyclic di-AMP. Accumulation of cyclic di-AMP in a GdpP PgpH double mutant is toxic for the cells, and the cells respond to this accumulation by inactivation of the diadenylate cyclase CdaA
physiological function
overexpression of PdeA leads to marked decreases in growth rates, both in vitro and in infected macrophages. Deletion of pdeA affects bacterial response to acid stress and leads to increased expression of resuscitation-promoting factors. Mutants with altered levels of c-di-AMP have different susceptibilities to peptidoglycan-targeting antibiotics
physiological function
both phosphodiesterases, GdpP and PgpH, contribute to the degradation of cyclic di-AMP. Accumulation of cyclic di-AMP in a GdpP PgpH double mutant is toxic for the cells, and the cells respond to accumulation by inactivation of the diadenylate cyclase CdaA
physiological function
DhhP is essential for Borrelia burgdorferi growth both in vitro and in the mammalian host. The conditional DhhP mutant has a dramatic increase in intracellular c-di-AMP level in comparison to the isogenic wild-type strain. Elevated cellular c-di-AMP in Borrelia burgdorferi does not result in an increased resistance to beta-lactamase antibiotics. The DhhP mutant is defective in induction of the sigmaS factor, RpoS, and the RpoS-dependent outer membrane virulence factor OspC
physiological function
-
disruption of gdpP increases intracellular c-di-AMP level and affects growth and increases biofilm formation. The GdpP mutant strain exhibits a significant decrease in hemolytic activity and adherence to and invasion of HEp-2 cells compared with the parental strain. Virulence genes cps2,sly, fpbs, mrp, ef and gdh display reduced expression in the gdpP mutant. In murine infection models, the GdpP mutant strain is attenuated, and impaired bacterial growth is observed in specific organs
physiological function
-
GdpP mutant bacteria contain extra-membranous material at the division sites and in the form of vesicles in the cytoplasm. Expression of superoxide dismutase SodM is 5fold downregulated in the mutant, while no significant differences in the susceptibility to H2O2 or in peroxide levels are observed
physiological function
inactivation of GdpP confers tolerance to inhibitors of peptidoglycan biosynthesis
physiological function
mutations in GdpP result in stable heat resistance and in some cases salt-hypersensitive phenotypes. Mutants display improved growth in response to sublethal concentrations of penicillin G. High-temperature incubation of a wild-type industrial Lactococcus lactis strain also results in spontaneous mutation GdpP and heat-resistant and salt-hypersensitive phenotypes. Acidification of milk by the GdpP-altered strain is inhibited by lower salt concentrations than the parent strain
physiological function
deficiency of Pde significantly enhances intracellular C12-C20 fatty acid accumulation. Superfluous c-di-AMP in Mycobacterium smegmatis may lead to abnormal colonial morphology
physiological function
the DHH/DHHA1 domain hydrolyzes c-di-AMP and c-di-GMP to generate the linear dinucleotides 5'-pApA and 5'-pGpG. The atypical GGDEF domain of YybT exhibits ATPase activity. YybT participates in DNA damage and acid resistance
physiological function
-
the contrasting activities of the enzymes diadenylate cyclase and phosphodiesterase determine the equilibrium levels of c-di-AMP
physiological function
-
both phosphodiesterases, GdpP and PgpH, contribute to the degradation of cyclic di-AMP. Accumulation of cyclic di-AMP in a GdpP PgpH double mutant is toxic for the cells, and the cells respond to this accumulation by inactivation of the diadenylate cyclase CdaA
-
physiological function
-
both phosphodiesterases, GdpP and PgpH, contribute to the degradation of cyclic di-AMP. Accumulation of cyclic di-AMP in a GdpP PgpH double mutant is toxic for the cells, and the cells respond to accumulation by inactivation of the diadenylate cyclase CdaA
-
physiological function
-
the DHH/DHHA1 domain hydrolyzes c-di-AMP and c-di-GMP to generate the linear dinucleotides 5'-pApA and 5'-pGpG. The atypical GGDEF domain of YybT exhibits ATPase activity. YybT participates in DNA damage and acid resistance
-
physiological function
-
inactivation of GdpP confers tolerance to inhibitors of peptidoglycan biosynthesis
-
physiological function
-
mutations within the GdpP gene, allow both laboratory and clinical isolates of Staphylococcus aureus to grow without lipoteichoic acid. Intracellular c-di-AMP levels increase drastically in GdpP deletion strains and in an lipoteichoic acid-deficient suppressor strain. An increased amount of cross-linked peptidoglycan is observed in the GdpP mutant strain. GdpP mutant strains display a 13-22% reduction in the cell size due to increased c-di-AMP levels
-
physiological function
-
deficiency of Pde significantly enhances intracellular C12-C20 fatty acid accumulation. Superfluous c-di-AMP in Mycobacterium smegmatis may lead to abnormal colonial morphology
-
physiological function
-
the contrasting activities of the enzymes diadenylate cyclase and phosphodiesterase determine the equilibrium levels of c-di-AMP
-
physiological function
-
a Pde2 mutant strain displays a growth defect in the early growth phase. Mutation leads to an increase in cellular c-di-AMP and 5'-O-phosphonoadenylyl-(3'->5')-adenosine levels and increased resistance to oxacillin
-
physiological function
-
overexpression of PdeA leads to marked decreases in growth rates, both in vitro and in infected macrophages. Deletion of pdeA affects bacterial response to acid stress and leads to increased expression of resuscitation-promoting factors. Mutants with altered levels of c-di-AMP have different susceptibilities to peptidoglycan-targeting antibiotics
-
physiological function
Lactococcus cremoris MG1363
-
mutations in GdpP result in stable heat resistance and in some cases salt-hypersensitive phenotypes. Mutants display improved growth in response to sublethal concentrations of penicillin G. High-temperature incubation of a wild-type industrial Lactococcus lactis strain also results in spontaneous mutation GdpP and heat-resistant and salt-hypersensitive phenotypes. Acidification of milk by the GdpP-altered strain is inhibited by lower salt concentrations than the parent strain
-
physiological function
-
DhhP is essential for Borrelia burgdorferi growth both in vitro and in the mammalian host. The conditional DhhP mutant has a dramatic increase in intracellular c-di-AMP level in comparison to the isogenic wild-type strain. Elevated cellular c-di-AMP in Borrelia burgdorferi does not result in an increased resistance to beta-lactamase antibiotics. The DhhP mutant is defective in induction of the sigmaS factor, RpoS, and the RpoS-dependent outer membrane virulence factor OspC
-
physiological function
-
disruption of gdpP increases intracellular c-di-AMP level and affects growth and increases biofilm formation. The GdpP mutant strain exhibits a significant decrease in hemolytic activity and adherence to and invasion of HEp-2 cells compared with the parental strain. Virulence genes cps2,sly, fpbs, mrp, ef and gdh display reduced expression in the gdpP mutant. In murine infection models, the GdpP mutant strain is attenuated, and impaired bacterial growth is observed in specific organs
-
additional information
CnpB has strong immunogenicity and induces high levels of humoral response and lung mucosal immunity after Mycobacterium tuberculosis intranasally infection
additional information
-
CnpB has strong immunogenicity and induces high levels of humoral response and lung mucosal immunity after Mycobacterium tuberculosis intranasally infection
-
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PGPH_LISM4
Listeria monocytogenes serotype 1/2a (strain 10403S)
718
7
81112
Swiss-Prot
other Location (Reliability: 2)
PDEA_LISM4
Listeria monocytogenes serotype 1/2a (strain 10403S)
657
1
74847
Swiss-Prot
-
GDPP_GEOTN
Geobacillus thermodenitrificans (strain NG80-2)
658
1
73706
Swiss-Prot
-
PGPH_BACSU
Bacillus subtilis (strain 168)
711
8
79167
Swiss-Prot
other Location (Reliability: 4)
W4QQT7_HALA3
Halalkalibacter akibai (strain ATCC 43226 / DSM 21942 / CIP 109018 / JCM 9157 / 1139)
313
0
34694
TrEMBL
-
A0A0H2XFX6_STAA3
Staphylococcus aureus (strain USA300)
313
0
35097
TrEMBL
-
A0A0H2ZNP2_STRP2
Streptococcus pneumoniae serotype 2 (strain D39 / NCTC 7466)
311
0
34967
TrEMBL
-
A0A0H2ZQZ4_STRP2
Streptococcus pneumoniae serotype 2 (strain D39 / NCTC 7466)
657
0
73275
TrEMBL
other Location (Reliability: 3)
A0QVM9_MYCS2
Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155)
340
0
35536
TrEMBL
-
A2RM60_LACLM
Lactococcus lactis subsp. cremoris (strain MG1363)
654
0
74055
TrEMBL
-
O51564_BORBU
Borreliella burgdorferi (strain ATCC 35210 / DSM 4680 / CIP 102532 / B31)
320
0
36190
TrEMBL
Secretory Pathway (Reliability: 2)
NRNA_MYCTU
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
336
0
35415
Swiss-Prot
Secretory Pathway (Reliability: 2)
Q2G2T6_STAA8
Staphylococcus aureus (strain NCTC 8325 / PS 47)
655
0
73781
TrEMBL
other Location (Reliability: 1)
Q8YAR3_LISMO
Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e)
657
0
74847
TrEMBL
-
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
protein possesses two transmembrane helices, a PAS domain, an atypical GGDEF domain, a DHH domain, and a DHHA1 domain
additional information
protein possesses two transmembrane helices, a PAS domain, an atypical GGDEF domain, a DHH domain, and a DHHA1 domain
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
solution structure of the small Per-ARNT-Sim domain. The domain adopts the characteristic PAS fold composed of a five-stranded antiparallel beta-sheet and a few short alpha-helices
crystal structure of the DHH/DHHA1 domain of GdpP, i.e. GdpP-C, and structures in complex with c-di-AMP, cyclic diguanosine monophosphate, and 5'-O-phosphonoadenylyl-(3'->5')-adenosine
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D420A
mutant exhibits residual activity against c-di-AMP, c-di-GMP, bis-p-nitrophenol phosphate, and thymidine monophosphate p-nitrophenol ester
D420A
-
mutant exhibits residual activity against c-di-AMP, c-di-GMP, bis-p-nitrophenol phosphate, and thymidine monophosphate p-nitrophenol ester
-
D130A/H131A
D134a/H135A/H136A
mutation in DHH domain, complete loss of catalytic activity
G313A/G314A/G315A/H316A
mutation in DHHA1 domain, mutasnt displays residual activity
D134a/H135A/H136A
-
mutation in DHH domain, complete loss of catalytic activity
-
G313A/G314A/G315A/H316A
-
mutation in DHHA1 domain, mutasnt displays residual activity
-
G266D
natural mutation identified in a strain displaying tolerance to inhibitors of peptidoglycan biosynthesis
T260K
natural mutation identified in a strain displaying tolerance to inhibitors of peptidoglycan biosynthesis
G266D
-
natural mutation identified in a strain displaying tolerance to inhibitors of peptidoglycan biosynthesis
-
T260K
-
natural mutation identified in a strain displaying tolerance to inhibitors of peptidoglycan biosynthesis
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression of GdpP is regulated by a cis-acting antisense RNA in vivo. Transcription of this antisense RNA is initiated in the middle of the GdpP gene and is dependent on an alternative sigma factor, sigmaD. Changes in sigmaD activity can modulate GdpP protein levels by about2.5fold
expression of GdpP is regulated by a cis-acting antisense RNA in vivo. Transcription of this antisense RNA is initiated in the middle of the GdpP gene and is dependent on an alternative sigma factor, sigmaD. Changes in sigmaD activity can modulate GdpP protein levels by about2.5fold
expression of GdpP is regulated by a cis-acting antisense RNA in vivo. Transcription of this antisense RNA is initiated in the middle of the GdpP gene and is dependent on an alternative sigma factor, sigmaD. Changes in sigmaD activity can modulate GdpP protein levels by about2.5fold
-
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
a truncation in the cyclic diadenosine monophosphate phosphodiesterase enzyme, GdpP, is identified in 7 of the 10 Austrian isolates and 10 of the 11 UK clinical isolates of beta-lactam resistant Staphylococcus aureus. Complementation of four representative isolates with an intact copy of the GdpP gene restored susceptibility to penicillins and abolished the growth defects caused by the truncation
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Witte, C.E.; Whiteley, A.T.; Burke, T.P.; Sauer, J.D.; Portnoy, D.A.; Woodward, J.J.
Cyclic di-AMP is critical for Listeria monocytogenes growth, cell wall homeostasis, and establishment of infection
mBio
4
e00282-13
2013
Listeria monocytogenes (Q8YAR3), Listeria monocytogenes, Listeria monocytogenes ATCC BAA-679 (Q8YAR3)
brenda
Gundlach, J.; Mehne, F.M.; Herzberg, C.; Kampf, J.; Valerius, O.; Kaever, V.; Stuelke, J.
An essential poison: synthesis and degradation of cyclic di-AMP in Bacillus subtilis
J. Bacteriol.
197
3265-3274
2015
Bacillus subtilis (P37484), Bacillus subtilis (P46344), Bacillus subtilis 168 (P37484), Bacillus subtilis 168 (P46344)
brenda
Griffiths, J.; ONeill, A.
Loss of function of the GdpP protein leads to joint beta-lactam/ glycopeptide tolerance in Staphylococcus aureus
Antimicrob. Agents Chemother.
56
579-581
2012
Staphylococcus aureus (Q2G2T6), Staphylococcus aureus NCTC 8325 (Q2G2T6)
brenda
Smith, W.M.; Pham, T.H.; Lei, L.; Dou, J.; Soomro, A.H.; Beatson, S.A.; Dykes, G.A.; Turner, M.S.
Heat resistance and salt hypersensitivity in Lactococcus lactis due to spontaneous mutation of llmg_1816 (gdpP) induced by high-temperature growth
Appl. Environ. Microbiol.
78
7753-7759
2012
Lactococcus cremoris (A2RM60), Lactococcus cremoris MG1363 (A2RM60)
brenda
Wang, F.; He, Q.; Su, K.; Wei, T.; Xu, S.; Gu, L.
Structural and biochemical characterization of the catalytic domains of GdpP reveals a unified hydrolysis mechanism for the DHH/DHHA1 phosphodiesterase
Biochem. J.
475
191-205
2018
Staphylococcus aureus (A0A0U1MUE2)
brenda
Ye, M.; Zhang, J.J.; Fang, X.; Lawlis, G.B.; Troxell, B.; Zhou, Y.; Gomelsky, M.; Lou, Y.; Yang, X.F.
DhhP, a cyclic di-AMP phosphodiesterase of Borrelia burgdorferi, is essential for cell growth and virulence
Infect. Immun.
82
1840-1849
2014
Borreliella burgdorferi (O51564), Borreliella burgdorferi, Borreliella burgdorferi DSM 4680 (O51564)
brenda
Tang, Q.; Luo, Y.; Zheng, C.; Yin, K.; Ali, M.; Li, X.; He, J.
Functional analysis of a c-di-AMP-specific phosphodiesterase MsPDE from Mycobacterium smegmatis
Int. J. Biol. Sci.
11
813-824
2015
Mycolicibacterium smegmatis (A0QVM9), Mycolicibacterium smegmatis ATCC 700084 (A0QVM9)
brenda
Ba, X.; Kalmar, L.; Hadjirin, N.F.; Kerschner, H.; Apfalter, P.; Morgan, F.J.; Paterson, G.K.; Girvan, S.L.; Zhou, R.; Harrison, E.M.; Holmes, M.A.
Truncation of GdpP mediates beta-lactam resistance in clinical isolates of Staphylococcus aureus
J. Antimicrob. Chemother.
74
1182-1191
2019
Staphylococcus aureus
brenda
Bai, Y.; Yang, J.; Eisele, L.E.; Underwood, A.J.; Koestler, B.J.; Waters, C.M.; Metzger, D.W.; Bai, G.
Two DHH subfamily 1 proteins in Streptococcus pneumoniae possess cyclic di-AMP phosphodiesterase activity and affect bacterial growth and virulence
J. Bacteriol.
195
5123-5132
2013
Streptococcus pneumoniae D39 (A0A0H2ZNP2), Streptococcus pneumoniae D39 (A0A0H2ZQZ4)
brenda
Rao, F.; See, R.; Zhang, D.; Toh, D.; Ji, Q.; Liang, Z.
YybT is a signaling protein that contains a cyclic dinucleotide phosphodiesterase domain and a GGDEF domain with ATPase activity
J. Biol. Chem.
285
473-482
2010
Bacillus subtilis (P37484), Bacillus subtilis 168 (P37484)
brenda
Tan, E.; Rao, F.; Pasunooti, S.; Pham, T.H.; Soehano, I.; Turner, M.S.; Liew, C.W.; Lescar, J.; Pervushin, K.; Liang, Z.X.
Solution structure of the PAS domain of a thermophilic YybT protein homolog reveals a potential ligand-binding site
J. Biol. Chem.
288
11949-11959
2013
Geobacillus thermodenitrificans (A4ITV2), Geobacillus thermodenitrificans NG80-2 (A4ITV2)
brenda
Corrigan, R.M.; Bowman, L.; Willis, A.R.; Kaever, V.; Gruendling, A.
Cross-talk between two nucleotide-signaling pathways in Staphylococcus aureus
J. Biol. Chem.
290
5826-5839
2015
Staphylococcus aureus
brenda
Bowman, L.; Zeden, M.S.; Schuster, C.F.; Kaever, V.; Gruendling, A.
New insights into the cyclic di-adenosine monophosphate (c-di-AMP) degradation pathway and the requirement of the cyclic dinucleotide for acid stress resistance in Staphylococcus aureus
J. Biol. Chem.
291
26970-26986
2016
Staphylococcus aureus (A0A0H2XFX6), Staphylococcus aureus USA300 (A0A0H2XFX6)
brenda
Du, B.; Ji, W.; An, H.; Shi, Y.; Huang, Q.; Cheng, Y.; Fu, Q.; Wang, H.; Yan, Y.; Sun, J.
Functional analysis of c-di-AMP phosphodiesterase, GdpP, in Streptococcus suis serotype 2
Microbiol. Res.
169
749-758
2014
Streptococcus suis, Streptococcus suis serotype 2
brenda
Luo, Y.; Helmann, J.D.
A sigmaD-dependent antisense transcript modulates expression of the cyclic-di-AMP hydrolase GdpP in Bacillus subtilis
Microbiology
158
2732-2741
2012
Bacillus subtilis (P37484), Bacillus subtilis 168 (P37484)
brenda
Cho, K.; Kang, S.
Streptococcus pyogenes c-di-AMP phosphodiesterase, GdpP, influences SpeB processing and virulence
PLoS ONE
8
e69425
2013
Streptococcus pyogenes
brenda
Manikandan, K.; Sabareesh, V.; Singh, N.; Saigal, K.; Mechold, U.; Sinha, K.
Two-step synthesis and hydrolysis of cyclic di-AMP in Mycobacterium tuberculosis
PLoS ONE
9
e86096
2014
Mycobacterium tuberculosis (P71615), Mycobacterium tuberculosis H37Rv (P71615)
brenda
Corrigan, R.; Abbott, J.; Burhenne, H.; Kaever, V.; Gruendling, A.
C-di-amp is a new second messenger in staphylococcus aureus with a role in controlling cell size and envelope stress
PLoS Pathog.
7
e1002217
2011
Staphylococcus aureus, Staphylococcus aureus RN4220
brenda
Commichau, F.M.; Heidemann, J.L.; Ficner, R.; Stuelke, J.
Making and breaking of an essential poison the cyclases and phosphodiesterases that produce and degrade the essential second messenger cyclic di-AMP in bacteria
J. Bacteriol.
201
e00462-18
2019
Staphylococcus aureus (A0A0U1MUE2)
brenda
Lu, Y.; Ning, H.; Kang, J.; Bai, G.; Zhou, L.; Kang, Y.; Wu, Z.; Tian, M.; Zhao, J.; Ma, Y.; Bai, Y.
Cyclic-di-AMP phosphodiesterase elicits protective immune responses against Mycobacterium tuberculosis H37Ra infection in mice
Front. Cell. Infect. Microbiol.
12
871135
2022
Mycobacterium tuberculosis (P71615), Mycobacterium tuberculosis ATCC 25618 (P71615)
brenda
Cabezas, A.; Costas, M.J.; Canales, J.; Pinto, R.M.; Rodrigues, J.R.; Ribeiro, J.M.; Cameselle, J.C.
Enzyme characterization of pro-virulent SntA, a cell wall-anchored protein of Streptococcus suis, with phosphodiesterase activity on cyclic-di-AMP at a level suited to limit the innate immune system
Front. Microbiol.
13
843068
2022
Streptococcus suis (Q8VUN9), Streptococcus suis CCUG 7984 (Q8VUN9)
brenda
Shang, Y.; Guo, J.; Zhao, Y.; Chen, J.; Meng, Q.; Qu, D.; Zheng, J.; Yu, Z.; Wu, Y.; Deng, Q.
Clemastine inhibits the biofilm and hemolytic of Staphylococcus aureus through the GdpP protein
Microbiol. Spectr.
10
e0054121
2022
Staphylococcus aureus, Staphylococcus aureus SA113
brenda
Gautam, S.; Mahapa, A.; Yeramala, L.; Gandhi, A.; Krishnan, S.; Kutti R., V.; Chatterji, D.
Regulatory mechanisms of c-di-AMP synthase from Mycobacterium smegmatis revealed by a structure Function analysis
Protein Sci.
32
e4568
2023
Mycolicibacterium smegmatis, Mycolicibacterium smegmatis ATCC 700084
brenda
EXTERNAL LINKS (specific for EC-Number 3.1.4.59)
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