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Literature summary extracted from

  • Kall, S.L.; Delikatny, E.J.; Lavie, A.
    Identification of a unique inhibitor-binding site on choline kinase alpha (2018), Biochemistry, 57, 1316-1325 .
    View publication on PubMed

Application

EC Number Application Comment Organism
2.7.1.32 drug development choline kinase is a promising target for development of inhibitors and inhibition of tumor growth Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.7.1.32 gene CHKA, recombinant expression of His-SUMO-tagged wild-type and mutant enzymes in Escherichia coli strain Rosetta (DE3)pLysS Homo sapiens

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.7.1.32 purified recombinant isozyme ChoKalpha truncated mutant DELTA79 in apoform and in complex with inhibitor TCD-717, sitting drop vapor diffusion method, mixing of 0.002 ml of 10 mg/ml protein solution with 0.002 ml of reservoir solution containing 0.1 M MES, pH 6.5, and 20% PEG 3350, 2-3 days, 20°C, crystals are soaked with TCD-717 by mixing a 50 mM solution of 100% DMSO-resuspended compound in a 1:4 ratio with the reservoir buffer, X-ray diffraction structure determination and analysis at 2.35 A resolution Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
2.7.1.32 additional information construction of enzyme N-terminally truncated mutant ChoKalpha1-DELTA79, inhibitor TCD-717 binding structure, overview Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.7.1.32 (1-azabicyclo[2.2.2]octan-3-yl)bis(5-chlorothiophen-2-yl)methanol
-
 Homo sapiens
2.7.1.32 (1S)-1-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-3-[2-[(oxan-4-yl)oxy]phenyl]-1-phenylpropan-1-ol
-
 Homo sapiens
2.7.1.32 1,1'-[butane-1,4-diylbis[(4,1-phenylene)methylene]]bis[4-(dimethylamino)pyridin-1-ium]
-
 Homo sapiens
2.7.1.32 1-[(4-[4-[4-([4-[(4-chlorophenyl)(methyl)amino]pyridin-1-ium-1-yl]methyl)phenyl]butyl]phenyl)methyl]-4-(dimethylamino)pyridin-1-ium
-
 Homo sapiens
2.7.1.32 1-[[4-[4-[[4-(4-chloro-N-methylanilino)quinolin-1-ium-1-yl]methyl]phenyl]phenyl]methyl]-N-(4-chlorophenyl)-N-methylquinolin-1-ium-4-amine i.e. TCD-717 or RSM-932A, strong inhibition of ChoKalpha, TCD-717 does not bind directly in the choline pocket but rather in a proximal location near the surface of the enzyme. Most notably, residues Tyr148, Ala176, Met177, Glu180, Phe200, Pro201, Trp248, Thr252, Tyr256, Glu332, Tyr333, Phe341, and Leu419 serve to orient and hold TCD-717 in place. Interaction of TCD-717 with ChoKalpha is driven by hydrophobic interactions across the N- and C-terminal domains. Binding of TCD-717 induces conformational changes compared to the unbound ChoKalpha structure. TCD-717 has completed phase I clinical trials Homo sapiens
2.7.1.32 6-amino-3-[(4'-[[4-(dimethylamino)pyridin-1-ium-1-yl]methyl][1,1'-biphenyl]-4-yl)methyl]-9H-purin-3-ium
-
 Homo sapiens
2.7.1.32 hemicholinium-3 HC-3 Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.7.1.32 additional information
-
 additional information steady-state kinetics Homo sapiens

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.7.1.32 Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.1.32 ATP + choline Homo sapiens
-
 ADP + phosphocholine
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.7.1.32 Homo sapiens P35790
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
2.7.1.32 recombinant His-SUMO-tagged wild-type and mutant enzymes from Escherichia coli strain Rosetta (DE3)pLysS by nickel affinity chromatography, and dialysis, if necessary the tag is cleaved, followd by another nickel affinity chromatography step, and dialysis, the last step for all is gel filtration Homo sapiens

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.7.1.32 carcinoma cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.1.32 ATP + choline
-
 Homo sapiens ADP + phosphocholine
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.7.1.32 choline kinase alpha
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.7.1.32 37
-
 assay at Homo sapiens

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
2.7.1.32 4.5
-
 ATP wild-type enzyme ChoKalpha, pH 7.5, 37°C Homo sapiens
2.7.1.32 26.5
-
 ATP recombinant mutant ChoKalphaDELTA79, pH 7.5, 37°C Homo sapiens
2.7.1.32 71
-
 choline wild-type enzyme ChoKalpha, pH 7.5, 37°C Homo sapiens
2.7.1.32 91.1
-
 choline recombinant mutant ChoKalphaDELTA79, pH 7.5, 37°C Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.7.1.32 7.5
-
 assay at Homo sapiens

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
2.7.1.32 0.00052
-
 wild-type enzyme ChoKalpha, pH 7.5, 37°C Homo sapiens 1-[[4-[4-[[4-(4-chloro-N-methylanilino)quinolin-1-ium-1-yl]methyl]phenyl]phenyl]methyl]-N-(4-chlorophenyl)-N-methylquinolin-1-ium-4-amine

General Information

EC Number General Information Comment Organism
2.7.1.32 physiological function choline kinase alpha (ChoKalpha) is an enzyme that is upregulated in many types of cancer and has been shown to be tumorigenic Homo sapiens