Protein Ser/Thr phosphatases of parasitic protozoa

Abstract

Protein phosphorylation is an important mechanism implicated in physiology of any organism, including parasitic protozoa. Enzymes that control protein phosphorylation (kinases and phosphatases) are considered promising targets for drug development. This review attempts to provide the first account of the current understanding of the structure, regulation and biological functions of protein Ser/Thr phosphatases in unicellular parasites. We have examined the complements of phosphatases ("phosphatomes") of the PPP and PPM families in several species of Apicomplexa (including malaria parasite Plasmodium), as well as Giardia lamblia, Entamoeba histolytica, Trichomonas vaginalis and a microsporidium Encephalitozoon cuniculi. Apicomplexans have homologues (in most cases represented by single isoforms) of all human PPP subfamilies. Some apicomplexan PPP phosphatases have no orthologues in their vertebrate hosts, including a previously unrecognised group of pseudo-phosphatases with putative Ca(2+)-binding domains, which we designate as EFPP. We also describe the presence of previously undetected Zn finger motifs in PPEF phosphatases from kinetoplastids, and a likely case of convergent evolution of tetratricopeptide repeat domain-containing phosphatases in G. lamblia. Among the parasites examined, E. cuniculi has the smallest Ser/Thr phosphatome (5 PPP and no PPM), while T. vaginalis shows the largest expansion of the PPP family (169 predicted phosphatases). Most protozoan PPM phosphatases cluster separately from human sequences. The structural peculiarities or absence of human orthologues of a number of protozoan protein Ser/Thr phosphatases makes them potentially suitable targets for chemotherapy and thus warrants their functional assessment.