Cofactors

There are no Cofactors for this Enzyme

Reaction Mechanism

adenosine kinase By Reference

Toxoplasma gondii adenosine kinase catalyses the transfer of phosphoryl group from ATP to adenosine to yield AMP and ADP. It belongs to the family of carbohydrate kinases. Like all parasitic protozoans, Toxoplasma gondii cannot synthesise purine bases de novo, so enzymes of the Toxoplasma gondii purine salvage pathway are required for parasite survival. Adenosine Kinase is one of the most important enzymes involved in this pathway. Therefore it represents an attractive target for drugs which attack this highly dangerous parasite.




• Summary
• Step 1
• Step 2
• Products

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 S_N2-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.

Catalytic Residues

AA	Uniprot	Uniprot Resid	PDB	PDB Resid
Asp	Q9TVW2	318	1lij	318
Arg	Q9TVW2	136	1lij	136

Step Components

overall product formed, proton transfer, overall reactant used, bimolecular nucleophilic substitution, native state of enzyme regenerated, inferred reaction step



Step 1.

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.



Step 2.

Water deprotonates Asp318 in an inferred return step.



Products.

The products of the reaction.

View Reaction Mechanisms in M-CSA

Reaction Parameters

There are no kinetic parameters information for this Enzyme

Associated Proteins

Citations

• 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.