188.8.131.52 - Adenosine kinase
There are no alternative names for this Enzyme
denosine + ATP = ADP + AMP + H(+)
There are no Cofactors for this Enzyme
Upon adenosine binding, a conserved dipeptide Gly68-Gly69 at the active site triggers a rigid-body rotation of 30 degrees of the lid domain, resulting in occlusion of the adenosine and the gamma-phosphate of ATP from the solvent. The reaction is ordered with adenosine binding first. This binding results in structural changes which are required in order for ATP to bind. The binding of ATP induces the formation of an anion hole, which completes the structural requirements for catalysis [PMID:10801355]. Asn223 and Glu226 are important in magnesium ion and phosphate binding.
The reaction proceeds through a single step SN2-like mechanism with nucleophilic attack on the gamma phosphate of ATP by the 3C OH of the ribose sugar, facilitated by deprotonation of the OH by Asp 318. The beta and gamma phosphate groups are in an eclipsed conformation, which results in a sterically and energetically strained state, thus aiding in pentavalent transition state formation [PMID:10801355] which is stabilised by Arg 136 and a Mg(II) ion.
|AA||Uniprot||Uniprot Resid||PDB||PDB Resid|
overall product formed, proton transfer, overall reactant used, bimolecular nucleophilic substitution, native state of enzyme regenerated, inferred reaction step
Asp318 deprotonates the -CH2-OH group of the adenosine substrate, which initiates a nucleophilic substitution against the gamma-phosphate of ATP. The adenosine 5'-hydroxyl group is positioned optimally for an in-line nucleophilic attack on the ATP gamma-phosphate atom. Asp318 is the likely candidate for proton abstraction of the 5'-hydroxyl group.
There are no kinetic parameters information for this Enzyme
- Developmental and foliation changes due to dysregulation of adenosine kinase in the cerebellum.
- Ectopic expression of neuronal adenosine kinase, a biomarker in mesial temporal lobe epilepsy without hippocampal sclerosis.
- Corrigendum: Adenosine kinase on deoxyribonucleic acid methylation: Adenosine receptor-independent pathway in cancer therapy.
- Reactive A1 Astrocyte-Targeted Nucleic Acid Nanoantiepileptic Drug Downregulating Adenosine Kinase to Rescue Endogenous Antiepileptic Pathway.
- Relationship between the Gene Expression of Adenosine Kinase Isoforms and the Expression of CD39 and CD73 Ectonucleotidases in Colorectal Cancer.
- Hepatocyte Adenosine Kinase Promotes Excessive Fat Deposition and Liver Inflammation.
- Deep brain stimulation suppresses epileptic seizures in rats via inhibition of adenosine kinase and activation of adenosine A1 receptors.
- Adenosine kinase promotes post-infarction cardiac repair by epigenetically maintaining reparative macrophage phenotype.
- Case Report: Adenosine kinase deficiency diagnosed 10 years after liver transplantation: Novel phenotypic insights.
- Adenosine-Metabolizing Enzymes, Adenosine Kinase and Adenosine Deaminase, in Cancer.
- Adenosine Kinase on Deoxyribonucleic Acid Methylation: Adenosine Receptor-Independent Pathway in Cancer Therapy.