Flavodiiron Protein from Trichomonas vaginalis Hydrogenosomes: the Terminal Oxygen Reductase

Abstract

Trichomonas vaginalis is one of a few eukaryotes that have been found to encode several homologues of flavodiiron proteins (FDPs). Widespread among anaerobic prokaryotes, these proteins are believed to function as oxygen and/or nitric oxide reductases to provide protection against oxidative/nitrosative stresses and host immune responses. One of the T. vaginalis FDP homologues is equipped with a hydrogenosomal targeting sequence and is expressed in the hydrogenosomes, oxygen-sensitive organelles that participate in carbohydrate metabolism and assemble iron-sulfur clusters. The bacterial homologues characterized thus far have been dimers or tetramers; the trichomonad protein is a dimer of identical 45-kDa subunits, each noncovalently binding one flavin mononucleotide. The protein reduces dioxygen to water but is unable to utilize nitric oxide as a substrate, similarly to its closest homologue from another human parasite Giardia intestinalis and related archaebacterial proteins. T. vaginalis FDP is able to accept electrons derived from pyruvate or NADH via ferredoxin and is proposed to play a role in the protection of hydrogenosomes against oxygen.

Flavodiiron Oxygen Reductase from Entamoeba histolytica

“…Consequently, for this variant, there are only two possible populations of each monomer: one with the fully loaded catalytic center and another population depleted of iron, thus inactive. The WT EhFdp1 exhibits in the mixed valence (Fe 3ϩ Fe 2ϩ ) state an EPR spectrum similar to that observed for other FDPs, with g values below 2.0 (11,20,37,46). In the course of the titration (Fig.…”

“…4C). The EPR spectra for WT and K53D EhFdp1 are clearly rhombic, similar to one another and to those of the E. coli, G. intestinalis, and T. vaginalis FDPs (20,37,46). Major differences were observed in the shape and g values of the Y271S and K53D/Y271S mutants, which exhibit quasi-axial spectra, with g max ϳ g med Ͼ Ͼ g min .…”

“…In pathogens, FDPs were suggested to enable survival in the hostile environment encountered during host infection, contributing to the detoxification of O 2 , particularly in the gut (10,11), and of NO produced by the host immune response (12)(13)(14)(15)(16). Although most known FDPs are encoded in the genomes of prokaryotes, several examples are found in multicellular and unicellular eukaryotes (6,10,(17)(18)(19)(20)(21). Among the latter, the enzymes from the anaerobic protozoan pathogens Giardia intestinalis (10), Trichomonas vaginalis (20), and Entamoeba histolytica (Fdp1) (11) have been investigated.…”

“…Although most known FDPs are encoded in the genomes of prokaryotes, several examples are found in multicellular and unicellular eukaryotes (6,10,(17)(18)(19)(20)(21). Among the latter, the enzymes from the anaerobic protozoan pathogens Giardia intestinalis (10), Trichomonas vaginalis (20), and Entamoeba histolytica (Fdp1) (11) have been investigated.…”

Giardia intestinalis Incorporates Heme into Cytosolic Cytochrome b 5

“…In addition, common hemoproteins (oxidases, catalases, and hydrolases) that are involved in oxidative-stress management in aerobes are replaced by different protective enzymes that were likely acquired by the anaerobic protists through lateral gene transfer from anaerobic bacteria. These enzymes include flavodiiron protein, hydroperoxide reductase, rubrerythrin, and NADH oxidase (9)(10)(11). The anaerobic protists were previously hypothesized to live entirely without heme (12), which may be true for Entamoeba histolytica, because no gene encoding any hemoprotein has been identified in the Entamoeba genome.…”