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Information on EC 3.6.1.1 - inorganic diphosphatase and Organism(s) Bacillus subtilis and UniProt Accession P37487
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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: Bacillus subtilis
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
-
-
-
-
inorganic diphosphatase
-
-
-
-
inorganic pyrophosphatase
-
-
-
-
PPase
-
-
-
-
pyrophosphatase, inorganic
-
-
-
-
Pyrophosphate phospho-hydrolase
-
-
-
-
Pyrophosphate phosphohydrolase
-
-
-
-
Pyrophosphate-energized inorganic pyrophosphatase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphorous acid anhydride hydrolysis
-
-
-
-
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
-
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
imidodiphosphate + H2O
phosphate + phosphoramidic acid
active site and substrate binding structure determination and analysis, overview
-
-
?
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
diphosphate + H2O
2 phosphate
-
actual substrate is magnesium diphosphate or dimagnesium diphosphate
-
-
?
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
-
actual substrate is magnesium diphosphate or dimagnesium diphosphate
-
-
?
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
Fe3+
bound in in sites M1 and M2, the Fe3+:Mn2+ ratio is about 6:1 in site M1 and about 2:1 in site M2
Mn2+
Mn2+
additional information
Mn2+
bound in in sites M1 and M2, the Fe3+:Mn2+ ratio is about 6:1 in site M1 and about 2:1 in site M2
additional information
the enzyme contains a unique trinuclear metal center, detailed structure analysis, overview. Mn2+ and Fe3+ do not exchange for Mg2+ even in the presence of a large excess of Mg2+
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 the enzyme 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 Bacillus subtilis. 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)
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. Structure-function analysis of canonical Family II PPases, catalytic reaction mechanism, detailed, overview
-
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
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
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
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
metal-binding sites are found in the DHH domain, whereas the substrate recruits ligands from both domains
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant wild-type and mutant enzymes in complex with substrate analogue imidodiphosphate, PNP, and/or inhibitor fluoride, 35-40 mg/ml protein in 83mM TES/K+, pH 7.2, 17 mM KCl and 0.05 mM EGTA is mixed with 5 mM MgCl2 and 10 mM NaF, 1 mM PNP, sitting drop vapour diffusion method, 4°C, 3:2 ratio of protein to well solution, the latter containing 100 mM HEPES/K+, pH 7.5, 2.3-2.5 M ammonium sulfate, 3-4% PEG 400, 2-3 days, X-ray diffraction structure determination and anaylsis at 1.75-2.15 A resolution, the mutant H98Q crystals do not contain fluoride ions
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
H98Q
the mutant shows highly reduced activity compared to the wild-type enzyme, crystal structure determination and comparison of substrate/inhibitor binding to the wild-type enzyme
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Tono, H.; Kornberg, A.
Biochemical studies of bacterial sporulation. III. Inorganic pyrophosphatase of vegetative cells and spores of Bacillus subtilis
J. Biol. Chem.
242
2375
1967
Bacillus subtilis
Kuhn, N.J.; Ward, S.
Purification, properties, and multiple forma of a manganese-activated inorganic pyrophosphatase from Bacillus subtilis
Arch. Biochem. Biophys.
354
47-56
1998
Bacillus subtilis
Fabrichniy, I.P.; Lehtioe, L.; Tammenkoski, M.; Zyryanov, A.B.; Oksanen, E.; Baykov, A.A.; Lahti, R.; Goldman, A.
A trimetal site and substrate distortion in a family II inorganic pyrophosphatase
J. Biol. Chem.
282
1422-1431
2007
Bacillus subtilis (P37487)
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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