Enzyme mechanism and slow-onset inhibition of Plasmodium falciparum enoyl-acyl carrier protein reductase by an inorganic complex

Patrícia Soares De Maria De Medeiros, Rodrigo G. Ducati, Luiz Augusto Basso, Diógenes Santiago Santos, Luiz Hildebrando Pereira Da Silva

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Malaria continues to be a major cause of children's morbidity and mortality worldwide, causing nearly one million deaths annually. The human malaria parasite, Plasmodium falciparum, synthesizes fatty acids employing the Type II fatty acid biosynthesis system (FAS II), unlike humans that rely on the Type I (FAS I) pathway. The FAS II system elongates acyl fatty acid precursors of the cell membrane in Plasmodium. Enoyl reductase (ENR) enzyme is a member of the FAS II system. Here we present steady-state kinetics, pre-steady-state kinetics, and equilibrium fluorescence spectroscopy data that allowed proposal of P. falciparum ENR (PfENR) enzyme mechanism. Moreover, building on previous results, the present study also evaluates the PfENR inhibition by the pentacyano(isoniazid)ferrateII compound. This inorganic complex represents a new class of lead compounds for the development of antimalarial agents focused on the inhibition of PfENR.

Original languageEnglish (US)
Article number642758
JournalEnzyme Research
Volume2011
Issue number1
DOIs
StatePublished - 2011
Externally publishedYes

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Acyl Carrier Protein
Plasmodium falciparum
Oxidoreductases
Fatty Acids
Enzymes
Lead compounds
Child Mortality
Kinetics
Plasmodium
Falciparum Malaria
Fluorescence Spectrometry
Biosynthesis
Isoniazid
Fluorescence spectroscopy
Antimalarials
Cell membranes
Malaria
Parasites
Cell Membrane
Morbidity

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

De Maria De Medeiros, P. S., Ducati, R. G., Basso, L. A., Santos, D. S., & Da Silva, L. H. P. (2011). Enzyme mechanism and slow-onset inhibition of Plasmodium falciparum enoyl-acyl carrier protein reductase by an inorganic complex. Enzyme Research, 2011(1), [642758]. https://doi.org/10.4061/2011/642758

Enzyme mechanism and slow-onset inhibition of Plasmodium falciparum enoyl-acyl carrier protein reductase by an inorganic complex. / De Maria De Medeiros, Patrícia Soares; Ducati, Rodrigo G.; Basso, Luiz Augusto; Santos, Diógenes Santiago; Da Silva, Luiz Hildebrando Pereira.

In: Enzyme Research, Vol. 2011, No. 1, 642758, 2011.

Research output: Contribution to journalArticle

De Maria De Medeiros, Patrícia Soares ; Ducati, Rodrigo G. ; Basso, Luiz Augusto ; Santos, Diógenes Santiago ; Da Silva, Luiz Hildebrando Pereira. / Enzyme mechanism and slow-onset inhibition of Plasmodium falciparum enoyl-acyl carrier protein reductase by an inorganic complex. In: Enzyme Research. 2011 ; Vol. 2011, No. 1.
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