Literature summary for 2.7.1.127 extracted from

Gonzalez, B.; Schell, M.J.; Letcher, A.J.; Veprintsev, D.B.; Irvine, R.F.; Williams, R.L.
Structure of a human inositol 1,4,5-trisphosphate 3-kinase: substrate binding reveals why it is not a phosphoinositide 3-kinase (2004), Mol. Cell, 15, 689-701.

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Activating Compound

Activating Compound	Comment	Organism	Structure
Calmodulin	i.e. CaM, regulatory function, in concert with Ca2+	Homo sapiens

Cloned(Commentary)

Cloned (Comment)	Organism
expression of His6-tagged fragment comprising residues 151-461 in Escherichia coli, expression of wild-type and mutant cDNA fragments encoding for residues 187-461 of the catalytic domain of isozyme A as unlabeled or selenomethionine-labeled GST fusion proteins in Escherichia coli strains C41(DE3) and B834(DE3)	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified recombinant unlabeled or selennomethionine-labeled wild-type and mutant catalytic domain residues 187-461 free or complexed to ATP, substrate, and product, automated sitting drop vapour diffusion method, 17°C, 0.001 ml protein solution over reservoir solution containing 0.83-0.85 M tri-sodium citrate, 0.1 M Tris-HCl, pH 8.0, and 0.1 M NaCl, heavy atom derivative, substrates, or products complex formation by addition and removal of 0.001 ml of 2 M Li2SO4 and 100 mM Tris-HCl, pH 8.0, 4°C, containing the relevant compound, i.e. 3 mM ATP, 3 mM MnCl2, or 5 mM 1D-myo-inositol 1,3,4,5-tetrakisphosphate, for 7times, and final soaking for 2.5 h, X-ray diffraction structure determination and analysis at 1.8-1.9 A resolution	Homo sapiens

Crystallization (Comment)

Organism

purified recombinant unlabeled or selennomethionine-labeled wild-type and mutant catalytic domain residues 187-461 free or complexed to ATP, substrate, and product, automated sitting drop vapour diffusion method, 17°C, 0.001 ml protein solution over reservoir solution containing 0.83-0.85 M tri-sodium citrate, 0.1 M Tris-HCl, pH 8.0, and 0.1 M NaCl, heavy atom derivative, substrates, or products complex formation by addition and removal of 0.001 ml of 2 M Li2SO4 and 100 mM Tris-HCl, pH 8.0, 4°C, containing the relevant compound, i.e. 3 mM ATP, 3 mM MnCl2, or 5 mM 1D-myo-inositol 1,3,4,5-tetrakisphosphate, for 7times, and final soaking for 2.5 h, X-ray diffraction structure determination and analysis at 1.8-1.9 A resolution

Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
A187S	crystal structure determination and analysis	Homo sapiens
D262A	14% of wild-type enzyme activity	Homo sapiens
D262N	12% of wild-type enzyme activity	Homo sapiens
D416A	inactive mutant	Homo sapiens
K199A	80% of wild-type enzyme activity	Homo sapiens
R391A	0.5% of wild-type enzyme activity	Homo sapiens
R391D	inactive mutant	Homo sapiens
W188A	44% of wild-type enzyme activity	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
1D-myo-inositol 1,4,5-trisphosphate	substrate inhibition of the catalytic domain	Homo sapiens

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Ca2+	regulatory function in concert with calmodulin	Homo sapiens
Mg2+	-	Homo sapiens

Natural Substrates/ Products (Substrates)

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

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	isozyme A	-

Purification (Commentary)

Purification (Comment)	Organism
His6-tagged fragment comprising residues 151-461 from Escherichia coli by nickel affinity chromatography, unlabeled or selenomethionine-labeled recombinant residues 185-459 of the catalytic domain of isozyme A fused to GST from Escherichia coli by glutathione affinity chromatography, removal of the GST-tag by recombinant TEV protease, further purification by a heparin affinity chromatography, and gel filtration	Homo sapiens

Purification (Comment)

Organism

His6-tagged fragment comprising residues 151-461 from Escherichia coli by nickel affinity chromatography, unlabeled or selenomethionine-labeled recombinant residues 185-459 of the catalytic domain of isozyme A fused to GST from Escherichia coli by glutathione affinity chromatography, removal of the GST-tag by recombinant TEV protease, further purification by a heparin affinity chromatography, and gel filtration

Homo sapiens

Reaction

Reaction	Comment	Organism	Reaction ID
ATP + 1D-myo-inositol 1,4,5-trisphosphate = ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate	catalytic mechanism, ATP, substrate and product binding	Homo sapiens	a

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
ATP + 1D-myo-inositol 1,4,5-trisphosphate	-	Homo sapiens	ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate	-	?
ATP + 1D-myo-inositol 1,4,5-trisphosphate	substrate and product binding site structure	Homo sapiens	ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate	-	?

Subunits

Subunits	Comment	Organism
More	the enzyme possesses a DCK264 motif, an IP-lobe G266-G329, and an IDFG motif	Homo sapiens

Synonyms

Synonyms	Comment	Organism
inositol 1,4,5-trisphosphate 3-kinase	-	Homo sapiens
More	the enzyme belongs tot he IPK family, structure comparisons	Homo sapiens

Cofactor

Cofactor	Comment	Organism	Structure
ATP	binding site structure, role of ATP-binding in the catalytic mechanism and substrate inhibition of the catalytic domain	Homo sapiens