are present in many organisms, including plants, bacteria, and the mitochondria of eukaryotes. However, these proteins belong to two unrelated protein families and are an example of convergent evolution. The plant-type FNRs (, ) include the plastidic FNRs seen in plants. The glutathione-reductase-type FNRs (, ), sometimes named adrenodoxin-NADP+ reductase for distinction, are seen in the mitochondria of eukaryotes. Both families are seen in bacteria. Two extra families, one thioredoxin reductase-like (TRLF) and the other with a unique mechanism (NfnAB), has been identified. In the plant-like family of FNRs, selective evolutionary pressure has led to differences in the catalytic efficiency of FNRs in photosynthetic and nonphotosynthetic organisms. Electron transfer by FNR is a rate limiting step in photosynthesis, so the plastidic FNR in plants have evolved to be highly efficient. These plastidic FNRs are 20–100 fold more active than bacterial FNRs. This higher catalytic efficiency of the transfer of electrons from FAD to NADP is related to structural changes in the active site that reduce the distance between the N5 in FAD and the C4 in NADP. The plastidic FNRs in plants have also evolved to have a high degree of substrate specificity for NADP over NAD; studies of amino acid mutations have shown that the terminal tyrosine residue in plastidic FNRs plays a key role in this substrate specificity. In contrast, some nonphotosynthetic FNRs do not preferentially bind NADP and lack this tyrosine residue. Disease relevance Several major human diseases are caused by the obligate intracellular protozoan parasites in the phylum Apicomplexa. The apicoplast organelle in these organisms is believed to have come from an endosymbiotic event in which an ancestral protozoan engulfed an algal cell. These apicoplasts contain plant-like FNRs that the protozoan uses to generate reduced ferredoxin, which is then used as a reductant in essential biosynthetic pathways. FNRs from two major parasites affecting humans, Plasmodium falciparum, which causes malaria, and Toxoplasma gondii, which causes toxoplasmosis, have been sequenced. Since humans do not have a homologous protein, these enzymes are possible new targets for drug therapies against these diseases. References Further reading External links EC 1.18.1 NADPH-dependent enzymes Flavoproteins Enzymes of known structure