Characterization of a new phosphatase from Plasmodium

Hills, T., Srivastava, A., Ayi, K., Wernimont, A.K., Kain, K., Waters, A.P. , Hui, R. and Pizarro, J.C. (2011) Characterization of a new phosphatase from Plasmodium. Molecular and Biochemical Parasitology, 179(2), pp. 69-79. (doi:10.1016/j.molbiopara.2011.06.001)

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Publisher's URL: http://dx.doi.org/10.1016/j.molbiopara.2011.06.001

Abstract

Plasmodium falciparum malaria is the most important parasitic disease worldwide, responsible for an estimated 1 million deaths annually. Two P. falciparum genes code for putative phosphoglycerate mutases (PGMases), a widespread protein group characterized by the involvement of histidine residues in their catalytic mechanism. PGMases are responsible for the interconversion between 2 and 3-phosphoglycerate, an intermediate step in the glycolysis pathway. We have determined the crystal structures of one of the P. falciparum's PGMases (PfPGM2) and a functionally distinct phosphoglycerate mutase from Cryptosporidium parvum, a related apicomplexan parasite. We performed sequence and structural comparisons between the two structures, another P. falciparum enzyme (PfPGM1) and several other PGM family members from other organisms. The comparisons revealed a distinct conformation of the catalytically active residues not seen in previously determined phosphoglycerate mutase structures. Furthermore, characterization of their enzymatic activities revealed contrasting behaviors between the PfPGM2 and the classical cofactor-dependent PGMase from C. parvum, clearly establishing PfPGM2 as a phosphatase with a residual level of mutase activity. Further support for this function attribution was provided by our structural comparison with previously characterized PGM family members. Genetic characterization of PGM2 in the rodent parasite Plasmodium berghei indicated that the protein might be essential to blood stage asexual growth, and a GFP tagged allele is expressed in both blood and zygote ookinete development and located in the cytoplasm. The P. falciparum PGM2 is either an enzyme implicated in the phosphate metabolism of the parasite or a regulator of its life cycle. (C) 2011 Elsevier B.V. All rights reserved

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Waters, Professor Andy and Srivastava, Mr Anubhav
Authors: Hills, T., Srivastava, A., Ayi, K., Wernimont, A.K., Kain, K., Waters, A.P., Hui, R., and Pizarro, J.C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Molecular and Biochemical Parasitology
Publisher:Elsevier BV
ISSN:0166-6851
ISSN (Online):1872-9428

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