Yuno Lee

Adenosine Kinase

adenosine• Nucleoside = adenine + ribose - β-N9-glycosidic bond.

• Energy transfer - adenosine triphosphate (ATP) - adenosine diphosphate (ADP)

• Signal transduction as cAMP.

AK(adenosine kinase)– Function

• ①ATP dependent phosphorylation of adenosine and other related nucleoside analogs to monophosphate derivatives. ②potential regulator of concentrations of extracellular adenosine and intracellular adenine nucleotides.

– Subunit• monomer (by similarity).

– Catalytic Activity• ATP + adenosine = ADP + AMP.

– Cofactor• binds 3 magnesium ions per subunit (by similarity).

AK(adenosine kinase)– Enzyme Regulation

• activity is inhibited by 5-iodotubercidin and 5'-amino-5'-deoxyadenosine (by similarity).

– Pathway• purine salvage.

– Tissue Specificity• highest expression in liver, testis, kidney and spleen. lower expression in brain. isoform long is predominant in testis and kidn

ey and isoform short is predominant in the spleen.

– Similarity• belongs to the carbohydrate kinase pfkb family.

FRONT BACK

ADO binding site

ATP binding site

ADO binding site

ATP binding site

Topology diagram of AK. The -helices (labeled 1- 12) and the -strands (labeled 1- 14).

ADO binding site

ADO binding site

ATP binding site

ATP binding site

(a) Stereodrawing of the adenosine 1 binding site.W:water(no tryptophan in here) , F:Phe, T:Thr, Q:Gln, D:Asp, N:Asn, G:Gly

(b) Stereodrawing of the adenosine 2 binding site.W:water(no tryptophan in here) , T:Thr, Q:Gln, D:Asp, G:Gly, H:His

Stereodiagram showing key active site residues and modeled (a) ATP and (b) Ap4A binding sites.

Stereodiagram showing key active site residues and modeled (a) ATP and (b) Ap4A binding sites.

References1. Biochemistry, 37 (45), 15607 -15620, 1998 Structure of Human

Adenosine Kinase at 1.5 Å Resolution