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Structure of glyceraldehyde-3-phosphate dehydrogenase from Plasmodium falciparum.

Satchell JF, Malby RL, Luo CS, Adisa A, Alpyurek AE, Klonis N, Smith BJ, Tilley L, Colman PM
Acta Crystallogr D Biol Crystallogr 61 1213-21 (2005)
Cited: 22 times
EuropePMC logo PMID: 16131754

Abstract

The malaria parasite Plasmodium falciparum is responsible for about two million deaths annually, making it important to obtain information about enzymes from this organism that represent potential drug targets. The gene for P. falciparum glyceraldehyde-3-phosphate dehydrogenase (PfGAPDH) has been cloned and the protein expressed as a hexahistidine-tagged recombinant protein in Escherichia coli. The recombinant protein has been crystallized and its three-dimensional structure determined. One molecule of the cofactor NAD+ is bound to each of the four subunits in the tetrameric enzyme. The major structural feature distinguishing human GAPDH from PfGAPDH is the insertion of a dipeptide (-KG-) in the so-called S loop. This insert, together with other characteristic single-amino-acid substitutions, alters the chemical environment of the groove that encompasses the R dyad and that links adjacent cofactor-binding sites and may be responsible for the selective inhibition of the enzyme by ferriprotoporphyrin IX.

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  4. Covalent Inhibitors of Plasmodium falciparum Glyceraldehyde 3-Phosphate Dehydrogenase with Antimalarial Activity in Vitro. Cullia G, Bruno S, Parapini S, Margiotta M, Tamborini L, Pinto A, Galbiati A, Mozzarelli A, Persico M, Paladino A, Fattorusso C, Taramelli D, Conti P. ACS Med Chem Lett 10 590-595 (2019)
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  7. The search for molecular mimicry in proteins carried by extracellular vesicles secreted by cells infected with Plasmodium falciparum. Armijos-Jaramillo V, Mosquera A, Rojas B, Tejera E. Commun Integr Biol 14 212-220 (2021)


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  3. Tracking Glideosome-associated protein 50 reveals the development and organization of the inner membrane complex of Plasmodium falciparum. Yeoman JA, Hanssen E, Maier AG, Klonis N, Maco B, Baum J, Turnbull L, Whitchurch CB, Dixon MW, Tilley L. Eukaryot Cell 10 556-564 (2011)
  4. Plasmodium glyceraldehyde-3-phosphate dehydrogenase: A potential malaria diagnostic target. Krause RGE, Hurdayal R, Choveaux D, Przyborski JM, Coetzer THT, Goldring JPD. Exp Parasitol 179 7-19 (2017)
  5. In silico prediction of antimalarial drug target candidates. Ludin P, Woodcroft B, Ralph SA, Mäser P. Int J Parasitol Drugs Drug Resist 2 191-199 (2012)
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  7. Effect of 3-bromopyruvate and atovaquone on infection during in vitro interaction of Toxoplasma gondii and LLC-MK2 cells. de Lima LP, Seabra SH, Carneiro H, Barbosa HS. Antimicrob Agents Chemother 59 5239-5249 (2015)
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  9. Biochemical characterisation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) from the liver fluke, Fasciola hepatica. Zinsser VL, Hoey EM, Trudgett A, Timson DJ. Biochim Biophys Acta 1844 744-749 (2014)
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  11. Computational study of glyceraldehyde-3-phosphate dehydrogenase of Entamoeba histolytica: implications for structure-based drug design. Kundu S, Roy D. J Biomol Struct Dyn 25 25-33 (2007)
  12. Phylogenetic and structural information on glyceraldehyde-3-phosphate dehydrogenase (G3PDH) in Plasmodium provides functional insights. Akinyi S, Gaona J, Meyer EV, Barnwell JW, Galinski MR, Corredor V. Infect Genet Evol 8 205-212 (2008)
  13. A Dual, Systematic Approach to Malaria Diagnostic Biomarker Discovery. Yerlikaya S, Owusu EDA, Frimpong A, DeLisle RK, Ding XC. Clin Infect Dis 74 40-51 (2022)


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