Ferredoxin--NADP(+) reductase (FNR)

Ferredoxin--NADP(+) reductase (FNR) is a flavin adenine dinucleotide (FAD)-dependent enzyme that facilitates the transfer of electrons between nicotinamide adenine dinucleotide phosphate (NADPH) and the iron-sulfur protein ferredoxin. In photosynthetic organisms, it is crucial for the final step of linear electron transport, while in non-photosynthetic organisms and the apicoplast of parasites, it operates in reverse to provide reducing power for essential biosynthetic pathways like isoprenoid and iron-sulfur cluster assembly. This enzyme is considered a major therapeutic target for treating infections caused by apicomplexan parasites, such as Plasmodium falciparum (malaria) and Toxoplasma gondii (toxoplasmosis), because the parasite version is plant-like and significantly different from the human mitochondrial ortholog, adrenodoxin reductase. In humans, the equivalent enzyme (FDXR) is vital for steroidogenesis and bile acid synthesis, and its dysfunction is linked to sensory neuropathies. Research into FNR inhibitors, including phenothiazines and various experimental compounds, aims to disrupt parasite metabolism while maintaining selectivity over the essential human enzyme. Consequently, FNR serves as a focal point for the development of novel antiparasitic agents with unique mechanisms of action.

Other names

Adrenodoxin reductaseFerredoxin reductaseFerredoxin--NADP(+) oxidoreductaseNADPH:adrenodoxin oxidoreductaseNADPH--ferredoxin reductasePlastidic-type ferredoxin--NADP(+) reductase

Enzyme inhibition that blocks electron transfer between NADPH and the FAD cofactor or prevents the productive protein-protein interaction between the reductase and ferredoxin.