Distinct subcellular localization in the cytosol and apicoplast, unexpected dimerization and inhibition of Plasmodium falciparum glyoxalases

Miriam Urscher, Jude M. Przyborski, Masaya Imoto, Marcel Deponte

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The ubiquitous glyoxalase system removes methylglyoxal as a harmful by-product of glycolysis. Because malaria parasites have drastically increased glycolytic fluxes, they could be highly susceptible to the inhibition of this detoxification pathway. Here we analysed the intracellular localization, oligomerization and inhibition of the glyoxalases from Plasmodium falciparum. Glyoxalase I (GloI) and one of the two glyoxalases II (cGloII) were located in the cytosol of the blood stages. The second glyoxalase II (tGloII) was detected in the apicoplast pointing to alternative metabolic pathways. Using a variety of methods, cGloII was found to exist in a monomer-dimer equilibrium that might have been overlooked for homologues from other organisms and that could be of physiological importance. The compounds methyl-gerfelin and curcumin, which were previously shown to inhibit mammalian GloI, also inhibited P. falciparum GloI. Inhibition patterns were predominantly competitive but were complicated because of the two different active sites of the enzyme. This effect was neglected in previous inhibition studies of monomeric glyoxalases I, with consequences for the interpretation of inhibition constants. In summary, the present work reveals novel general glyoxalase properties that future research can build on and provides a significant advance in characterizing the glyoxalase system from P. falciparum.

Original languageEnglish
Pages (from-to)92-103
Number of pages12
JournalMolecular Microbiology
Volume76
Issue number1
DOIs
Publication statusPublished - 2010

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Apicoplasts
Lactoylglutathione Lyase
Dimerization
Plasmodium falciparum
hydroxyacylglutathione hydrolase
Cytosol
Pyruvaldehyde
Curcumin
Glycolysis
Metabolic Networks and Pathways
Malaria
Catalytic Domain
Parasites
Enzymes

ASJC Scopus subject areas

  • Molecular Biology
  • Microbiology
  • Medicine(all)

Cite this

Distinct subcellular localization in the cytosol and apicoplast, unexpected dimerization and inhibition of Plasmodium falciparum glyoxalases. / Urscher, Miriam; Przyborski, Jude M.; Imoto, Masaya; Deponte, Marcel.

In: Molecular Microbiology, Vol. 76, No. 1, 2010, p. 92-103.

Research output: Contribution to journalArticle

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