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Characterization of a new phosphatase from Plasmodium.

Hills T, Srivastava A, Ayi K, Wernimont AK, Kain K, Waters AP, Hui R, Pizarro JC
Mol Biochem Parasitol 179 69-79 (2011)
Cited: 17 times
EuropePMC logo PMID: 21689687

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.

Reviews - 3eoz mentioned but not cited (1)

  1. Fragment-based cocktail crystallography by the medical structural genomics of pathogenic protozoa consortium. Verlinde CL, Fan E, Shibata S, Zhang Z, Sun Z, Deng W, Ross J, Kim J, Xiao L, Arakaki TL, Bosch J, Caruthers JM, Larson ET, Letrong I, Napuli A, Kelly A, Mueller N, Zucker F, Van Voorhis WC, Buckner FS, Merritt EA, Hol WG. Curr Top Med Chem 9 1678-1687 (2009)


Reviews citing this publication (3)

  1. From crystal to compound: structure-based antimalarial drug discovery. Drinkwater N, McGowan S. Biochem. J. 461 349-369 (2014)
  2. Exploiting unique structural and functional properties of malarial glycolytic enzymes for antimalarial drug development. Alam A, Neyaz MK, Ikramul Hasan S. Malar Res Treat 2014 451065 (2014)
  3. The Potential of Secondary Metabolites from Plants as Drugs or Leads against Protozoan Neglected Diseases-Part III: In-Silico Molecular Docking Investigations. Ogungbe IV, Setzer WN. Molecules 21 (2016)

Articles citing this publication (13)

  1. Discovery and analysis of cofactor-dependent phosphoglycerate mutase homologs as novel phosphoserine phosphatases in Hydrogenobacter thermophilus. Chiba Y, Oshima K, Arai H, Ishii M, Igarashi Y. J. Biol. Chem. 287 11934-11941 (2012)
  2. Genome wide in silico analysis of Plasmodium falciparum phosphatome. Pandey R, Mohmmed A, Pierrot C, Khalife J, Malhotra P, Gupta D. BMC Genomics 15 1024 (2014)
  3. Construction and validation of a detailed kinetic model of glycolysis in Plasmodium falciparum. Penkler G, du Toit F, Adams W, Rautenbach M, Palm DC, van Niekerk DD, Snoep JL. FEBS J. 282 1481-1511 (2015)
  4. Atypical mitogen-activated protein kinase phosphatase implicated in regulating transition from pre-S-Phase asexual intraerythrocytic development of Plasmodium falciparum. Balu B, Campbell C, Sedillo J, Maher S, Singh N, Thomas P, Zhang M, Pance A, Otto TD, Rayner JC, Adams JH. Eukaryotic Cell 12 1171-1178 (2013)
  5. Structural units important for activity of a novel-type phosphoserine phosphatase from Hydrogenobacter thermophilus TK-6 revealed by crystal structure analysis. Chiba Y, Horita S, Ohtsuka J, Arai H, Nagata K, Igarashi Y, Tanokura M, Ishii M. J. Biol. Chem. 288 11448-11458 (2013)
  6. Characterization of a Plasmodium berghei sexual stage antigen PbPH as a new candidate for malaria transmission-blocking vaccine. Kou X, Zheng W, Du F, Liu F, Wang M, Fan Q, Cui L, Luo E, Cao Y. Parasit Vectors 9 190 (2016)
  7. Functional characterization of Plasmodium berghei PSOP25 during ookinete development and as a malaria transmission-blocking vaccine candidate. Zheng W, Liu F, He Y, Liu Q, Humphreys GB, Tsuboi T, Fan Q, Luo E, Cao Y, Cui L. Parasit Vectors 10 8 (2017)
  8. A Prioritized and Validated Resource of Mitochondrial Proteins in Plasmodium Identifies Unique Biology. van Esveld SL, Meerstein-Kessel L, Boshoven C, Baaij JF, Barylyuk K, Coolen JPM, van Strien J, Duim RAJ, Dutilh BE, Garza DR, Letterie M, Proellochs NI, de Ridder MN, Venkatasubramanian PB, de Vries LE, Waller RF, Kooij TWA, Huynen MA. mSphere 6 e0061421 (2021)
  9. Structures of PGAM5 Provide Insight into Active Site Plasticity and Multimeric Assembly. Chaikuad A, Filippakopoulos P, Marcsisin SR, Picaud S, Schröder M, Sekine S, Ichijo H, Engen JR, Takeda K, Knapp S. Structure 25 1089-1099.e3 (2017)
  10. Crystallization and preliminary X-ray diffraction analysis of a novel type of phosphoserine phosphatase from Hydrogenobacter thermophilus TK-6. Chiba Y, Horita S, Ohtsuka J, Arai H, Nagata K, Igarashi Y, Tanokura M, Ishii M. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 68 911-913 (2012)
  11. Functional characterization of two members of histidine phosphatase superfamily in Mycobacterium tuberculosis. Coker OO, Warit S, Rukseree K, Summpunn P, Prammananan T, Palittapongarnpim P. BMC Microbiol. 13 292 (2013)
  12. Research Support, Non-U.S. Gov't Phosphatases are emerging as novel druggable targets in Plasmodium. Khalife J, Pierrot C. Future Microbiol 11 603-606 (2016)
  13. The tetrameric structure of Plasmodium falciparum phosphoglycerate mutase is critical for optimal enzymatic activity. Tehlan A, Bhowmick K, Kumar A, Subbarao N, Dhar SK. J Biol Chem 298 101713 (2022)


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