Adenosine kinase from Mycobacterium tuberculosis is the only prokaryotic
adenosine kinase that has been isolated and characterized. The
enzyme catalyzes the phosphorylation of
adenosine to
adenosine monophosphate and is involved in the activation of
2-methyladenosine, a compound that has demonstrated selective activity against M.
tuberculosis. The mechanism of action of
2-methyladenosine is likely to be different from those of current
tuberculosis treatments and this compound (or other
adenosine analogs) may prove to be a novel therapeutic intervention for this disease. The M.
tuberculosis adenosine kinase was overexpressed in Escherichia coli and the
enzyme was purified with activity comparable to that reported previously. The
protein was crystallized in the presence of
adenosine using the vapour-diffusion method. The crystals diffracted X-rays to high resolution and a complete data set was collected to 2.2 A using
synchrotron radiation. The crystal belonged to space group P3(1)21, with unit-cell parameters a = 70.2, c = 111.6 A, and contained a single
protein molecule in the asymmetric unit. An initial structural model of the
protein was obtained by the molecular-replacement method, which revealed a dimeric structure. The monomers of the dimer were related by twofold crystallographic symmetry. An understanding of how the M.
tuberculosis adenosine kinase differs from the human homolog should aid in the design of more potent and selective
antimycobacterial agents that are selectively activated by this
enzyme.