Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel protein phosphatase cDNA of the PPP superfamily was identified from the malaria parasite, Plasmodium falciparum (Pf), and tentatively named PfPPJ. The predicted primary structure of the phosphatase contained all the known conserved motifs of the PPP superfamily essential for catalytic activity. The enzyme was specific for dephosphorylation of phosphoserine and phosphothreonine residues with very little activity against phosphotyrosine residues. However, the sequence at its C-terminal end was unique, and was consistent with its resistance to the classical PP2A-specific inhibitors such as okadaic acid and microcystin-LR, and the PP1-specific inhibitor, mammalian heat-stable inhibitor-2 (I-2). Even the catalytic core of PfPPJ had a sequence substantially different from the other PPPs such that PfPPJ could be placed in an apparently separate phylogenetic branch. At 294 amino acids residues, PfPPJ was one of the smallest okadaic acid-resistant PPP phosphatases known. By Northern blot analysis, the expression of the PfPPJ mRNA showed the following pattern: schizont > ring > trophozoite, which closely paralleled the expression of the protein, as determined by immunofluorescence. Together, these results suggested a parasitic stage-specific transcriptional regulation of this novel and potentially unique protozoan phosphatase.
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PMID:Characterization of a novel serine/threonine protein phosphatase (PfPPJ) from the malaria parasite, Plasmodium falciparum. 1137 37

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.
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PMID:Protein Ser/Thr phosphatases of parasitic protozoa. 1861 95