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Literature summary for 2.7.4.24 extracted from

  • Wang, H.; Godage, H.Y.; Riley, A.M.; Weaver, J.D.; Shears, S.B.; Potter, B.V.
    Synthetic inositol phosphate analogs reveal that PPIP5K2 has a surface-mounted substrate capture site that is a target for drug discovery (2014), Chem. Biol., 21, 689-699.
    View publication on PubMedView publication on EuropePMC

Activating Compound

Activating Compound Comment Organism Structure
2,5-O-benzyl-myo-inositol 1,3,4,6-tetrakisphosphate activates the ATP hydrolysis activity and inhibits the InsP6 kinase activity of the enzyme Homo sapiens
2-O-aminoethyl-myo-inositol 1,2,3,4,6-pentakisphosphate
-
Homo sapiens
2-O-benzoyl-myo-inositol 1,2,3,4,6-pentakisphosphate
-
Homo sapiens
2-O-benzyl-5-O-alpha-phosphonoacetyl-myo-inositol 1,3,4,6-tetrakisphosphate stimulates ATP hydrolysis 9fold Homo sapiens
2-O-benzyl-5-O-diphosphate-myo-inositol 1,3,4,6-tetrakisphosphate
-
Homo sapiens
2-O-benzyl-myo-inositol 1,2,3,4,6-pentakisphosphate
-
Homo sapiens
2-O-butanoyl-myo-inositol 1,2,3,4,6-pentakisphosphate
-
Homo sapiens
5-O-alpha-diphosphate-myo-inositol 1,3,4,6-tetrakisphosphate
-
Homo sapiens
5-O-alpha-phoshonoacetyl-myo-inositol 1,3,4,6-tetrakisphosphate
-
Homo sapiens
5-O-alpha-phosphonoacetyl-myo-inositol 1,2,3,4,6-pentakisphosphate stimulates ATP hydrolysis 5fold Homo sapiens
additional information synthesis and effects of inositol phosphates and analogues upon ATPase activity, overview. The compounds are also inhibitors of [PP]2-InsP4 dephosphorylation. Binding structures, overview Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
recombinant expression of wild-type and mutant enzymes Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
N-terminally truncated PPIP5K2 kinase mutant, residues 41-366, hanging drop vapor diffusion against a well buffer of 12% w/v PEG 3350, 20 mM MgCl2, 0.1 M HEPES, pH 7.0, 0,1 mM AMP-PNP, and 2 mM CdCl2 at 4°C, 3 days, 4°C, X-ray diffraction structure determination and analysis Homo sapiens

Protein Variants

Protein Variants Comment Organism
E192G site-directed mutagenesis Homo sapiens
E192Q site-directed mutagenesis Homo sapiens
K103A site-directed mutagenesis Homo sapiens
K213A site-directed mutagenesis Homo sapiens
K54A site-directed mutagenesis Homo sapiens
additional information construction of an N-terminally truncated mutant PPIP5K2KD comprising residues 41-366 Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
2,5-O-benzyl-myo-inositol 1,3,4,6-tetrakisphosphate activates the ATP hydrolysis activity and inhibits the PPIP5K2 activity and InsP6 kinase activity, and the 1,5-[PP]2-InsP4 dephosphorylation activity of the enzyme. The compound can inhibit inositol phosphate kinase activity without occupying the catalytic site Homo sapiens
2-O-benzyl-5-O-alpha-phosphonoacetyl-myo-inositol 1,3,4,6-tetrakisphosphate stimulates ATP hydrolysis 9fold, but inhibits 1,5-[PP]2-InsP4 dephosphorylation activity of the enzyme. The compound can inhibit inositol phosphate kinase activity without occupying the catalytic site Homo sapiens
2-O-benzyl-5-O-diphosphate-myo-inositol 1,3,4,6-tetrakisphosphate activates ATP hydrolysis activity but inhibits 1,5-[PP]2-InsP4 dephosphorylation activity of the enzyme Homo sapiens
2-O-benzyl-myo-inositol 1,2,3,4,6-pentakisphosphate activates ATP hydrolysis activity but inhibits 1,5-[PP]2-InsP4 dephosphorylation activity of the enzyme Homo sapiens
5-O-alpha-diphosphate-myo-inositol 1,3,4,6-tetrakisphosphate activates ATP hydrolysis activity but inhibits 1,5-[PP]2-InsP4 dephosphorylation activity of the enzyme Homo sapiens
5-O-alpha-phosphonoacetyl-myo-inositol 1,2,3,4,6-pentakisphosphate stimulates ATP hydrolysis 5fold, but inhibits 1,5-[PP]2-InsP4 dephosphorylation activity of the enzyme Homo sapiens
additional information synthesis and effects of inositol phosphates and analogues upon ATPase activity, overview. The compounds are also inhibitors of [PP]2-InsP4 dephosphorylation. Binding structures, overview Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + 1D-myo-inositol 5-diphosphate 1,2,3,4,6-pentakisphosphate Homo sapiens
-
ADP + 1D-myo-inositol 1,5-bis(diphosphate) 2,3,4,6-tetrakisphosphate
-
?
ATP + 1D-myo-inositol hexakisphosphate Homo sapiens
-
ADP + 1D-myo-inositol 1-diphosphate 2,3,4,5,6-pentakisphosphate
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens O43314 isozyme PPIP5K2
-

Purification (Commentary)

Purification (Comment) Organism
recombinant wild-type and truncated mutant enzymes Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + 1D-myo-inositol 5-diphosphate 1,2,3,4,6-pentakisphosphate
-
Homo sapiens ADP + 1D-myo-inositol 1,5-bis(diphosphate) 2,3,4,6-tetrakisphosphate
-
?
ATP + 1D-myo-inositol hexakisphosphate
-
Homo sapiens ADP + 1D-myo-inositol 1-diphosphate 2,3,4,5,6-pentakisphosphate
-
?
additional information the bifunctional enzyme also catalyzes the reaction of EC 2.7.4.21, InsP6 kinase. The enzyme exhibits an unusual, nonproductive, substrate-stimulated ATPase activity, that is stimulated by the natural substrates and by 5-O-alpha-phosphonoacetyl-myo-inositol 1,2,3,4,6-pentakisphosphate and 2-O-benzyl-5-O-alpha-phosphonoacetyl-myo-inositol 1,3,4,6-tetrakisphosphate. It also shows 1,5-[PP]2-InsP4 dephosphorylation activity. The enzyme has two adjacent ligand-binding sites, the architecture of this second ligand-binding site is represented by a deep cleft, which is walled on one side by K53, K54, and K103. The opposite face is formed from R213, and a loop created from residues E192 to H194 Homo sapiens ?
-
?

Synonyms

Synonyms Comment Organism
diphosphoinositol pentakisphosphate kinase 2
-
Homo sapiens
More cf. EC 2.7.4.21 Homo sapiens
PPIP5K2
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7 7.5 assay at Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ATP
-
Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.00014
-
inhibition of the 1,5-[PP]2-InsP4 dephosphorylation, pH 7.0, 37°C Homo sapiens 5-O-alpha-phosphonoacetyl-myo-inositol 1,2,3,4,6-pentakisphosphate
0.00017
-
inhibition of the 1,5-[PP]2-InsP4 dephosphorylation, pH 7.0, 37°C Homo sapiens 2,5-O-benzyl-myo-inositol 1,3,4,6-tetrakisphosphate
0.00042
-
inhibition of the 1,5-[PP]2-InsP4 dephosphorylation, pH 7.0, 37°C Homo sapiens 2-O-benzyl-5-O-alpha-phosphonoacetyl-myo-inositol 1,3,4,6-tetrakisphosphate
0.00044
-
inhibition of the 1,5-[PP]2-InsP4 dephosphorylation, pH 7.0, 37°C Homo sapiens 2-O-benzyl-myo-inositol 1,2,3,4,6-pentakisphosphate
0.0005
-
inhibition of the 1,5-[PP]2-InsP4 dephosphorylation, pH 7.0, 37°C Homo sapiens 2-O-benzyl-5-O-diphosphate-myo-inositol 1,3,4,6-tetrakisphosphate
0.0024
-
inhibition of the 1,5-[PP]2-InsP4 dephosphorylation, pH 7.0, 37°C Homo sapiens 5-O-alpha-diphosphate-myo-inositol 1,3,4,6-tetrakisphosphate