Mutational analysis of the Mycobacterium tuberculosis Rv1625c adenylyl cyclase: residues that confer nucleotide specificity contribute to dimerization.

The mycobacterial Rv1625c gene product is an adenylyl cyclase with sequence similarity to the mammalian enzymes. The catalytic domain of the enzyme forms a homodimer and residues specifying adenosine triphosphate (ATP) specificity lie at the dimer interface. Mutation of these residues to those present in guanylyl cyclases failed to convert the enzyme to a guanylyl cyclase, but dramatically reduced its adenylyl cyclase activity and altered its oligomeric state. Computational modeling revealed subtle differences in the dimer interface that could explain the biochemical data, suggesting that the structural and catalytic features of this homodimeric adenylyl cyclase are in contrast to those of the heterodimeric mammalian enzymes.