The ascent of nucleotide cyclases: conservation and evolution of a theme

Cyclic nucleotides are known to regulate a number of metabolic and developmental processes in all living organisms. There are two types of nucleotide cyclases, adenylyl cyclases that produce 3¢5¢- cyclic adenosine monophosphate (cAMP) and guanylyl cyclases that synthesize the corresponding guanosine (cGMP) analogue. Both enzymes utilize their respective nucleotide triphosphates as substrates, and require a metal co-factor, usually Mg or Mn, for catalysis (Tang and Hurley 1998). With information available from large scale genome sequencing projects, it is apparent that cyclases can be classified into different sub-classes, based on the amino acid sequence similarities, rather than their substrate specificities (see figure 1). Such a classification reveals interesting differences amongst these enzymes as a result of divergence in their structure