CyaG, a novel cyanobacterial adenylyl cyclase and a possible ancestor of mammalian guanylyl cyclases

A novel gene encoding an adenylyl cyclase, designated cyaG, was identified in the filamentous cyanobacterium Spirulina platensis, The predicted amino acid sequence of the C-terminal region of cyaG was similar to the catalytic domains of Class III adenylyl and guanylyl cyclases, The N-terminal region next to the catalytic domain of CyaG was similar to the dimerization domai n, which is highly conserved among guanylyl cyclases. As a whole, CyaG is m ore closely related to guanylyl cyclases than to adenylyl cyclases in its p rimary structure. The catalytic domain of CyaG was expressed in Escherichia coli and partially purified. CyaG showed adenylyl cyclase (but not guanyly l cyclase) activity. By site-directed mutagenesis of three amino acid resid ues (Lys(533), Ile(603), and Asp(605)) within the purine ring recognition s ite of CyaG to Glu, Arg, and Cys, respectively, CyaG was transformed to a g uanylyl cyclase that produced cGMP instead of cAMP. Thus having properties of both cyclases, CyaG may therefore represent a critical position in the e volution of Class III adenylyl and guanylyl cyclases.