Plasmodium falciparum glutathione reductase (GR)

Plasmodium falciparum glutathione reductase is a cytosolic, homodimeric flavoenzyme responsible for catalyzing the reduction of glutathione disulfide (GSSG) to reduced glutathione (GSH), maintaining a high GSH:GSSG ratio critical for parasite antioxidant defense and redox homeostasis[1][6][7]. The enzyme is structurally similar to its human counterpart but differs at several ligand-binding sites, including the glutathione-binding pocket and the dimer interface, offering opportunities for selective inhibition[1][3]. While not absolutely essential for asexual blood-stage development, it is implicated as a promising target for antimalarial drug design, particularly in blocking sexual development and malaria transmission[2][4]. Selective inhibition of this enzyme disrupts redox homeostasis, potentially sensitizing the parasite to oxidative stress and leading to therapeutic efficacy against malaria[3][4]. Methylene blue is one example of a drug interacting with the enzyme; new tricyclic inhibitors are under investigation for selective targeting[3]. The potential for off-target toxicity due to homology with the human enzyme is a challenge for drug development[1][3][4].

Other names

Glutathione reductasePfGRNADPH:glutathione oxidoreductase

Inhibition of glutathione disulfide reduction; Disruption of redox balance in parasite; Transmission-blocking by impairing parasite development