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Information on EC 3.6.1.1 - inorganic diphosphatase and Organism(s) Streptococcus gordonii and UniProt Accession P95765
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3.6.1.1 inorganic diphosphataseIUBMB Comments
Specificity varies with the source and with the activating metal ion. The enzyme from some sources may be identical with EC 3.1.3.1 (alkaline phosphatase) or EC 3.1.3.9 (glucose-6-phosphatase). cf. EC 7.1.3.1, H+-exporting diphosphatase.
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Word Map
- 3.6.1.1
- thiamine
- ppases
- vacuole
- apparatus
- nucleoside
-
tonoplast
- triphosphate
-
cytochemical
-
cisternae
- h+-atpase
- lysosome
- magnesium
- polyphosphate
- glucose-6-phosphatase
- orthophosphate
-
mung
- rubrum
-
cytochemistry
- rhodospirillum
- imidodiphosphate
-
saccule
-
nudix
-
h+-pumping
-
antiporter
- 5'-nucleotidase
-
proton-pumping
-
electrogenic
- vigna
- acpase
-
diadenosine
-
monophosphatase
- tripolyphosphate
-
v-type
- diphosphonate
- ap4a
-
chromatophores
-
dihydrate
- tetraphosphate
-
ectonucleotide
- exopolyphosphatase
-
vacuolar-type
- radiata
- phosphomonoesterase
- autotaxin
-
osmium
-
pyrophosphate-dependent
- n,n'-dicyclohexylcarbodiimide
-
decapping
-
pyrophosphohydrolase
-
sulfurylase
- molecular biology
- synthesis
The taxonomic range for the selected organisms is: Streptococcus gordonii
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
pyrophosphatase, inorganic pyrophosphatase, v-ppase, h+-ppase, vacuolar h(+)-pyrophosphatase, sppase, e-ppase, vacuolar h(+)-ppase, soluble inorganic pyrophosphatase, ippase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
H+-PPase
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-
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inorganic diphosphatase
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-
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inorganic pyrophosphatase
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-
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PPase
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-
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pyrophosphatase, inorganic
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-
-
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Pyrophosphate phospho-hydrolase
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-
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Pyrophosphate phosphohydrolase
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-
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Pyrophosphate-energized inorganic pyrophosphatase
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-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphorous acid anhydride hydrolysis
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-
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SYSTEMATIC NAME
IUBMB Comments
diphosphate phosphohydrolase
Specificity varies with the source and with the activating metal ion. The enzyme from some sources may be identical with EC 3.1.3.1 (alkaline phosphatase) or EC 3.1.3.9 (glucose-6-phosphatase). cf. EC 7.1.3.1, H+-exporting diphosphatase.
CAS REGISTRY NUMBER
COMMENTARY
9024-82-2
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
diphosphate + H2O
2 phosphate
the enzyme can also catalyze the reverse reaction of diphosphate synthesis from phosphate, but this activity does not seem physiologically important
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-
r
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
diphosphate + H2O
2 phosphate
the enzyme can also catalyze the reverse reaction of diphosphate synthesis from phosphate, but this activity does not seem physiologically important
-
-
r
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Ca2+, a strong antagonist of Mg2+ and inhibitor of all other PPases, can replace Mg2+ as activator of Mn2+-bound canonical Family II PPases, conferring about 10% of their maximal activity
Mg2+
Mn2+
additional information
soluble Family II PPase enzymes require both magnesium and a transition metal ion (manganese or cobalt) for maximal activity and are the most active among all PPase types. Catalysis by s requires four metal ions per substrate molecule, three of which form a unique trimetal center that coordinates the nucleophilic water and converts it to a reactive hydroxide ion. One or two additional sites that bind Mn2+ and Mg2+ with millimolar affinities have been detected in canonical Family II PPases of Streptococcus gordonii. An additional Mg2+ ion is brought to the enzyme as part of a Mg-phosphate complex, the true substrate. In the cell, Mg2+ ions appear to occupy all sites except that containing a transition metal ion
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
adenine nucleotide
a quarter of Family II PPases contain an autoinhibitory regulatory insert formed by two cystathionine beta-synthase (CBS) domains and one DRTGG domain. Adenine nucleotide binding either activates or inhibits the CBS domain-containing PPases, thereby tuning their activity and, hence, diphosphate levels, in response to changes in cell energy status (ATP/ADP ratio)
fluoride
inhibits Family I PPases at micromolar concentrations by replacing the nucleophilic water molecule. The effect of fluoride on Family II enzymes strongly depends on the metal cofactor in the tight binding site. Mn/Co enzymes are inhibited weakly by fluoride, but if the transition metal is replaced by Mg2+, fluoride binds 1000times tighter, achieving an affinity characteristic of Family I enzymes
additional information
C-substituted derivatives of methylene bisphosphonate, which are nonhydrolyzable diphosphate analogues, bind to Family II PPases 2-3 orders of magnitude more weakly than to Family I enzymes, whereas PNP binds with similar affinity, regardless of the metal cofactor bound
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.054
diphosphate
recombinant mutants I260V and I260E, pH 9.0, 25°C
additional information
additional information
kinetics of wild-type and mutant enzymes
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additional information
additional information
-
kinetics of wild-type and mutant enzymes
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
inorganic pyrophosphatases (PPases) are present in all cell types
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
physiological function
diphosphate, a byproduct and regulator of numerous biosynthetic reactions, is converted to metabolizable phosphate via the action of specific constitutive enzymes-inorganic pyrophosphatases (PPases). Soluble PPases convert diphosphate energy into heat, as opposed to membrane-bound PPases, which employ diphosphate energy to transport H+ or Na+ across membranes in plants and some bacteria, archaea, and protists. Both PPase types can also catalyze the reverse reaction of diphosphate synthesis from phosphate, but this activity does not seem physiologically important
additional information
evolution
soluble PPases belong to three nonhomologous families, of which family II is found in approximately a quarter of prokaryotic organisms, often pathogenic ones. Each subunit of dimeric canonical Family II PPases is formed by two domains connected by a flexible linker, with the active site located between the domains. The enzymes require both magnesium and a transition metal ion (manganese or cobalt) for maximal activity and are the most active among all PPase types. Soluble PPases convert diphosphate energy into heat, as opposed to membrane-bound PPases, which employ diphosphate energy to transport H+ or Na+ across membranes in plants and some bacteria, archaea, and protists. Soluble PPases belong to three nonhomologous families, I, II, and III. Family I PPases are found in all kingdoms of life, whereas Family II and Family III PPases are found in prokaryotes. Distribution of Family II PPases, overview
additional information
the hinge region plays an important role in opening and closing of the active site between the N- and C-terminal domains of PPase
additional information
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the hinge region plays an important role in opening and closing of the active site between the N- and C-terminal domains of PPase
additional information
metal-binding sites are found in the DHH domain, whereas the substrate recruits ligands from both domains. Structure-function analysis of canonical Family II PPases, catalytic reaction mechanism, detailed, overview
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
27000
1 x * 27000 + 1 * 57000, recombinant mutant I259V, native PAGE in absence of Mn2+, 1 * 32000 + 1 x 62000, recombinant wild-type enzyme, native PAGE in absence of Mn2+
32000
1 x * 27000 + 1 * 57000, recombinant mutant I259V, native PAGE in absence of Mn2+, 1 * 32000 + 1 x 62000, recombinant wild-type enzyme, native PAGE in absence of Mn2+
50000
recombinant mutant I259D, native PAGE, in absence of Mn2+
57000
1 x * 27000 + 1 * 57000, recombinant mutant I259V, native PAGE in absence of Mn2+, 1 * 32000 + 1 x 62000, recombinant wild-type enzyme, native PAGE in absence of Mn2+
60000
61000
recombinant mutant I260V, native PAGE, in absence of Mn2+
62000
recombinant mutant I260E, native PAGE, in presence of Mn2+
64000
recombinant mutant I260V, native PAGE, in presence of Mn2+
78000
recombinant wild-type enzyme, native PAGE, in presence of Mn2+
additional information
60000
recombinant mutant I260D, native PAGE, in presence or absence of Mn2+
60000
recombinant mutants I260E and I259E, native PAGE, in absence of Mn2+
additional information
the enzyme is ellipsoidal with an axial ratio of 3.37, which increases in absence of divalent cation to 3.94, analytical ultracentrifugation
additional information
-
the enzyme is ellipsoidal with an axial ratio of 3.37, which increases in absence of divalent cation to 3.94, analytical ultracentrifugation
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
additional information
dimer
1 x * 27000 + 1 * 57000, recombinant mutant I259V, native PAGE in absence of Mn2+, 1 * 32000 + 1 x 62000, recombinant wild-type enzyme, native PAGE in absence of Mn2+
dimer
each subunit of dimeric canonical Family II PPases is formed by two domains connected by a flexible linker, with the active site located between the domains. Canonical Family II PPases structures, domain structures, overview
additional information
the free N- and C-terminal domains do not interact productively, when mixed together, the interdomain region has the function of a mechanical hinge, structure modelling
additional information
-
the free N- and C-terminal domains do not interact productively, when mixed together, the interdomain region has the function of a mechanical hinge, structure modelling
additional information
the hinge region plays an important role in opening and closing of the active site between the N- and C-terminal domains of PPase. Family II PPases are dimer under physiological conditions with Mn2+ present, and may dissociate into monomers at low enzyme concentration in the absence of Mn2+
additional information
-
the hinge region plays an important role in opening and closing of the active site between the N- and C-terminal domains of PPase. Family II PPases are dimer under physiological conditions with Mn2+ present, and may dissociate into monomers at low enzyme concentration in the absence of Mn2+
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
G190A
site-directed mutagenesis, the mutant shows altered kinetic parameters and reduced activity compared to the wild-type enzyme
G190W
site-directed mutagenesis, the mutant shows altered kinetic parameters and reduced activity compared to the wild-type enzyme
I259V
site-directed mutagenesis, the mutant shows 20% reduced activity compared to the wild-type enzyme
I260D
site-directed mutagenesis, the mutant shows 86% reduced activity compared to the wild-type enzyme
I260E
site-directed mutagenesis, the mutant shows 89% reduced activity compared to the wild-type enzyme
I260V
site-directed mutagenesis, the mutant shows 20% increased activity compared to the wild-type enzyme, the mutant is activable by NaF in contrast to the wild-type enzyme
T191G
site-directed mutagenesis, the mutant shows altered kinetic parameters and reduced activity compared to the wild-type enzyme
additional information
additional information
construction of several deletion and insertion mutants, overview, mutants with altered interdomain region display 2-265fold decreased catalytic efficiency, overview
additional information
-
construction of several deletion and insertion mutants, overview, mutants with altered interdomain region display 2-265fold decreased catalytic efficiency, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant soluble wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by anion exchange and hydrophobic interaction chromatography
recombinant wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by anion exchange and hydrophobic interaction chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
overexpression of soluble wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ilias, M.; Young, T.W.
Streptococcus gordonii soluble inorganic pyrophosphatase: An important role for the interdomain region in enzyme activity
Biochim. Biophys. Acta
1764
1299-1306
2006
Streptococcus gordonii (P95765), Streptococcus gordonii, Streptococcus gordonii DL1 (P95765)
Ilias, M.; White, S.A.; Young, T.W.
Isoleucine 259 and isoleucine 260 residues in Streptococcus gordonii soluble inorganic pyrophosphatase play an important role in enzyme activity
J. Biosci. Bioeng.
112
8-13
2011
Streptococcus gordonii (P95765), Streptococcus gordonii, Streptococcus gordonii DL1 (P95765), Streptococcus gordonii DL1
Baykov, A.A.; Anashkin, V.A.; Salminen, A.; Lahti, R.
Inorganic pyrophosphatases of family II - two decades after their discovery
FEBS Lett.
591
3225-3234
2017
Desulfitobacterium hafniense (A0A098B5G4), Bacillus subtilis (P37487), Streptococcus gordonii (P95765), Papaver rhoeas (Q2P9V0), Clostridium perfringens (Q8XIQ9), Streptococcus agalactiae (R4ZBK7), Staphylococcus aureus (W8TS62), Clostridium perfringens type A (Q8XIQ9), Streptococcus gordonii V288 (P95765), Clostridium perfringens 13 (Q8XIQ9)
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