Plasmodium falciparum Serine/Threonine Phoshoprotein Phosphatases (PPP): From Housekeeper to the ‘Holy Grail’

Author(s): Joanna Bajsa, Stephen O. Duke, Babu L. Tekwani.

Journal Name: Current Drug Targets

Volume 9 , Issue 11 , 2008

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Abstract:

Availability of complete genome sequence for Plasmodium falciparum has been useful in drawing a comprehensive metabolic map of the parasite. Distinct and unique metabolic characteristics of the parasite may be exploited as potential targets for new antimalarial drug discovery research. Reversible phosphorylation of proteins is a ubiquitous process and an indispensable part of cell signaling cascades, which regulate different cellular functions. Not so long ago the role of protein phosphatases in the cell life was underestimated but now these enzymes strongly focus attention of many researches. Based on primary structure and functional characteristics protein phosphatases have been divided into number of families and subfamilies. The amino acid sequences of catalytic subunits of protein phosphatases of particular families stay highly conserved in eukaryotic organisms during evolutionary changes. Serine/threonine protein phosphatases (PPPs) constitute an important family, which are involved in mitotic and meiotic cell divisions, cell development, apoptosis and many other crucial cellular processes. Complex life cycle of the malaria parasite, which encompasses through distinct developmental stages, offers highly sophistical roles for the protein phosphatases. We have researched and analyzed characteristics of 17 putative or/and confirmed catalytic subunits of PPPs on P. falciparum genome. Evidences have been gathered that indicate functional expression of some PPP isoforms in P. falciparum. A few of them have been found to be essential or play important cellular functions in the parasite. Identification of distinct molecular and functional characteristics of these enzymes shall be useful in designing selective inhibitors of plasmodial PPPs as potential new antimalarials.

Keywords: Plasmodium falciparum, protozoa, serine/threonine protein phosphatase, protein dephosphorylation

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Article Details

VOLUME: 9
ISSUE: 11
Year: 2008
Page: [997 - 1012]
Pages: 16
DOI: 10.2174/138945008786786055
Price: $58

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