Adenosine kinase (ATP:adenosine 5 prime phosphotransferase) is an abundant enzyme in mammalian tissues that catalyzes the transfer of the gamma phosphate from ATP to adenosine, thereby serving as a potentially important regulator of concentrations of both extracellular adenosine and intracellular adenine nucleotides. Adenosine has widespread effects on the cardiovascular, nervous, respiratory, and immune systems and inhibitors of ADK could play an important pharmacological role in increasing intravascular adenosine concentrations and acting as antiinflammatory agents. The encoded protein does not present any sequence similarities to other well characterized mammalian nucleoside kinases. In contrast, 2 regions were identified with significant sequence identity to microbial ribokinase and fructokinases and a bacterial inosine/guanosine kinase. Thus, ADK is a structurally distinct mammalian nucleoside kinase that appears to be akin to sugar kinases of microbial origin.