Human Adenosine Kinase (ADK, EC

Synonyms: ADK, Adenosine 5'-phosphotransferase

NOVOCIB's human adenosine kinase is an active and purified, 345-aa short form(14,2) ADK protein (39kDa) cloned by RT-PCR amplification of mRNA extracted from human hepatoma cells and expressed in E.coli. The sequence of the cloned ADK (GenBank accession number U50196) was confirmed by DNA sequencing (100% identity)

Adenosine kinase is a key enzyme of nucleoside analogs activation
For rapid evaluation of substrates properties of novel nucleoside analogs for human adenosine kinase see our PRECICE® ADK Phosphorylation Assay Kit.

ADK is also a validated target for Drug Discovery: adenosine-regulating drugs have been extensively tested(1) as new analgesic and anti-inflammatory agents(4) to treat schizophrenia(7) or to limit brain injury after an ischemic stroke(8).

ADK Reaction schema

Adenosine Kinase

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Pricing updated December 8th, 2013.

Kit is provided in stable lyophilized form and shipped without dry ice

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Adenosine kinase is a ubiquitous enzyme that catalyzes the transfer of γ-phosphate from ATP to 5'-hydroxyl of adenosine (AR), an important modulator of central nervous system functions and a signal molecule involved in hypoxia, inflammation, and nociception. Together with adenosine deaminase, adenosine kinase regulates intra- and extracellular cellular adenosine concentration. Inhibition of adenosine kinase results in a selective increase of local adenosine concentrations and reduced seizure susceptibility and nociception in vivo(3). ADK dysfunction is involved in several pathologies, including diabetes(13), epilepsy(6), and cancer. Consequently, ADK emerges as a rational therapeutic target for Drug Discovery, and adenosine-regulating drugs have been extensively tested (1) as new analgesic and anti-inflammatory agents(4) to treat schizophrenia(7) or to limit brain injury after an ischemic stroke(8).
The X-ray crystallographic structure of human ADK has been described(9) and provides structural basis for rational design and optimisation of new ADK inhibitors. In addition, this enzyme is responsible for the phosphorylation and consequent clinical activity of several therapeutically useful nucleosides, including the antiviral drug ribavirin(10), immunosuppressive drug mizoribine(11), and anticancer C-nucleoside, tiazofurin(12).

AK Gel photo

Unit Definition: One unit of adenosine kinase converts 1.0 µmole of inosine and ATP to IMP and ADP per minute at pH 8 at 37°C, as measured by a coupled IMPDH enzyme system.
(see ADK Assay Kit for further details)

Specific Activity: ≥ 0.200 unit/mg protein.

Purity: controlled by 12% AA SDS-PAGE.

Assay condition: Enzymatic activity of adenosine kinase with particular nucleoside substrate is measured by spectrophotometric assays in a coupled lactate dehydrogenase / pyruvate kinase system. Assays were carried out at 37°C, at 50mM Tris-HCl pH7,6; 50mM KCl, 5mM MgCl2, 2.5mM ATP, 0.1mM NADH, 1mM phosphoenolpyruvate, 1mM DTT, PK 5U/ml, LDH 5U/ml. Reaction was followed in an iEMS Reader MF (Labsystems) microtiter plate reader at 340nm. Nucleosides, nucleotides, LDH and PK were purchased from Sigma-Aldrich.

AK Kinetics Graph
References (with external links to PubMed)
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  1. D. Boison (2013) Adenosine kinase: exploitation for therapeutic gain. Pharmacol Rev. 2013 Apr 16;65(3):906-43
  2. B. Sahin et al. (2004): Molecular characterization of recombinant mouse adenosine kinase and evaluation as a target for protein phosphorylation Eur. J. Biochem. 271(17), 3547-3555
  3. M. F. Jarvis et al. (2000): ABT-702 (4-amino-5-(3-bromophenyl)-7-(6-morpholinopyridin-3-yl)pyrido[2, 3-d]pyrimidine), a novel orally effective adenosine kinase inhibitor with analgesic and anti-inflammatory properties: I. In vitro characterization and acute antinociceptive effects in the mouse J. Pharmacol. Exp. Ther. 295(3), 1156-1164
  4. S. McGaraughty et al. (2005): Anticonvulsant and antinociceptive actions of novel adenosine kinase inhibitors Curr. Top. Med. Chem. 5(1):43-58
  5. D. E. Fedele et al. (2005): Astrogliosis in epilepsy leads to overexpression of adenosine kinase, resulting in seizure aggravation Brain 128(Pt 10), 2383-2395
  6. D. Boison (2008): The adenosine kinase hypothesis of epileptogenesis Prog. Neurobiol. 84(3), 249-262
  7. D. Boison et al. (2011): Adenosine hypothesis of schizophrenia Opportunities for pharmacotherapy doi:10.1016/J.neuropharm.2011.01.048
  8. H. Y. Shen et al. (2011): Adenosine kinase determines the degree of brain injury after ischemic stroke in mice J. Cereb. Blood Flow Metab. 31(7): 1648-1659
  9. I. I. Mathews et al. (1998): Structure of human adenosine kinase at 1.5 A resolution Biochemistry 37(45): 15607-602
  10. R. C. Willis et al. (1978): Adenosine kinase initiates the major route of ribavirin activation in a cultured human cell Proc. Natl. Acad. Sci. USA 75(7), 3042-3044
  11. R. L. Miller et al. (1979): Adenosine kinase from rabbit liver. II. Substrate and inhibitor specificity J. Biol. Chem., 254(7), 2346-2352
  12. P. P. Saunders et al. (1990): Tiazofurin is phosphorylated by three enzymes from Chinese hamster ovary cells Cancer Res. 50(17), 5269-5274
  13. J. Annes et al. (2012): Adenosine kinase inhibition selectively promotes rodent and porcine islet β-cell replication Proc. Natl. Acad. Sci. USA Vol: 109:3915-3920
  14. J. Spychala et al. (1996): Cloning of human adenosine kinase cDNA: Sequence similarity to microbial ribokinases and fructokinases Proc. Natl. Acad. Sci. USA 93(3), 1232-1237