Purine nucleotide cyclases in the malaria parasite

Cells use a variety of signal transduction pathways to coordinate their responses to changes in both the extracellular and intracellular environment. Activation of these pathways is often receptor mediated, resulting in the synthesis of second messenger molecules such as cAMP and cGMP. In Plasmodium falciparum, these cyclic nucleotides have been implicated in regulating sexual differentiation, an obligate stage in the parasite life cycle. cAMP and cGMP are synthesized by adenylyl cyclase and guanylyl cyclase, respectively, and in P. falciparum these enzymes differ significantly from their mammalian counterparts. In this article, we will discuss the properties of the parasite cyclases, with emphasis on their structure, function and evolutionary origin.