Information on EC 2.7.7.85 - diadenylate cyclase

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The expected taxonomic range for this enzyme is: Bacteria

EC NUMBER
COMMENTARY hide
2.7.7.85
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RECOMMENDED NAME
GeneOntology No.
diadenylate cyclase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
2 ATP = 2 diphosphate + cyclic di-3',5'-adenylate
show the reaction diagram
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SYSTEMATIC NAME
IUBMB Comments
ATP:ATP adenylyltransferase (cyclizing)
Cyclic di-3',5'-adenylate is a bioactive molecule produced by some bacteria and archaea, which may function as a secondary signalling molecule [1]. The intracellular bacterial pathogen Listeria monocytogenes secretes it into the host's cytosol, where it triggers a cytosolic pathway of innate immunity [2].
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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reduction of cyclic di-3',5'-adenylate levels by conditional depletion of the di-adenylate cyclase DacA leads to marked decreases in growth rates, both in vitro and in macrophages. Conditional depletion of dacA also leads to increased IFN-beta expression and a concomitant increase in host cell pyroptosis, a result of increased bacteriolysis and subsequent bacterial DNA release
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2 ADP
? + cyclic di-3',5'-adenylate
show the reaction diagram
2 ATP
2 diphosphate + cyclic di-3',5'-adenylate
show the reaction diagram
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
2 ATP
2 diphosphate + cyclic di-3',5'-adenylate
show the reaction diagram
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
D5TK88
the enzyme is strictly dependent on divalent cations, activity in presence of 10 mM Ca2+ is 10.6% compared to activity in presence of 10 mM Mg2+
Co2+
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or Mn2+, required. Maximum activity at 0.75-10 mM
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3'-dATP
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competitive inhibitor of the diadenylate cyclase domain, binds in the same position as ATP
Tannic acid
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inhibits both DisA and phosphodiesterase YybT
theaflavin-3'-gallate
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specifically inhibits DisA but not phosphodiesterase YybT
theaflavin-3,3'-digallate
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specifically inhibits DisA but not phosphodiesterase YybT
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.003
3'-dATP
Thermotoga maritima
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pH 9.5, 60°C
0.0236
theaflavin-3'-gallate
Bacillus subtilis
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pH 7.5, 30°C
0.0085
theaflavin-3,3'-digallate
Bacillus subtilis
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pH 7.5, 30°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8.5 - 10
D5TK88
pH 8.5: about 50% of maximal activity, pH 10.0: about 40% of maximal activity, CHES buffer
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
55
D5TK88
the enzyme exhibits the highest activity at 55°C for 30 min
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
45 - 65
D5TK88
45°C: about 65% of maximal activity, 65°C: about 30% of maximal activity
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
17000
and 37000 and 167000 Da, gel filtration
37000
and 167000 and 17000 Da, gel filtration
41100
D5TK88
x * 41100, calculated from sequence
42700
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2 * 42700
42900
8 * 42900
43000
D5TK88
x * 43000, SDS-PAGE
155000
gel filtration
167000
and 37000 and 17000 Da, gel filtration
300000
gel filtration
339000
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gel filtration, mutant D75N
353500
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analytical ultracentrifugation
370000
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gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hexamer
monomer
octamer
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
structure of N-terminally truncated protein lacking first 100 residues, i.e. the transmembrane domain and the CC motif, to 2.8 A resolution. The protein exhibits an overall globular fold with the long N-terminally located helix (alpha1) flanking the core
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crystallisation of apoenzyme, apoenzyme + ATPgammaS, apoenzyme + cordycepin-triphosphate, determination of the crystal structure at 2.1 A
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structure in the presence of 3'-dATP and Mn2+. The metal ion is octahedrally coordinated with all six coordination positions occupied by oxygen ligands. The three phosphate groups from 3'-dATP together with Asp75 from the adjacent subunit and two water molecules are all located between 2.0 and 2.5 A from the manganese. The pre-reaction state shows a highly coordinated arrangement of the two ATP (-analogues) in almost optimal distance for the nucleophilic attack of the 3'-OH on the alpha-phosphate of the neighbouring ATP. The rate-limiting step of cyclic di-AMP synthesis by DisA is not defined by the reaction itself, but rather by the accessibility of the active site
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
60
D5TK88
loss of activity above
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cdaA and cdaS genes are cloned into the expression vector pET28a, expression in Escherichia coli
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expression in Escherichia coli
expression of truncated CdaA variants in Escherichia coli
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overexpression of the C-terminal His-tagged protein in Escherichia coli
D5TK88
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A61V
11.6fold increase in cyclic di-AMP production
A76V
4.3fold increase in cyclic di-AMP production
E46K
19.5fold increase in cyclic di-AMP production
L44F
90.5fold increase in cyclic di-AMP production
P201Q
12.8fold increase in cyclic di-AMP production
A61V
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11.6fold increase in cyclic di-AMP production
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A76V
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4.3fold increase in cyclic di-AMP production
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E46K
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19.5fold increase in cyclic di-AMP production
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L44F
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90.5fold increase in cyclic di-AMP production
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additional information
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