title: Novel functions of an iron-sulfur flavoprotein from Trichomonas vaginalis hydrogenosomes.
abstract: Iron-sulfur flavoproteins (Isf) are flavin mononucleotide (FMN)- and FeS cluster-containing proteins commonly encountered in anaerobic prokaryotes. However, with the exception of Isf from Methanosarcina thermophila, which participates in oxidative stress management by removing oxygen and hydrogen peroxide, none of these proteins has been characterized in terms of function. Trichomonas vaginalis, a sexually transmitted eukaryotic parasite of humans, was found to express several iron-sulfur flavoprotein (TvIsf) homologs in its hydrogenosomes. We show here that in addition to having oxygen-reducing activity, the recombinant TvIsf also functions as a detoxifying reductase of metronidazole and chloramphenicol, both of which are antibiotics effective against a variety of anaerobic microbes. TvIsf can utilize both NADH and reduced ferredoxin as electron donors. Given the prevalence of Isf in anaerobic prokaryotes, we propose that these proteins are central to a novel defense mechanism against xenobiotics.
authors.affiliation: Department of Parasitology, Charles University in Prague, Prague, Czech Republic.
authors.forename: Tamara
authors.initials: T
authors.lastname: Smutná
authors.affiliation: Department of Parasitology, Charles University in Prague, Prague, Czech Republic.
authors.forename: Katerina
authors.initials: K
authors.lastname: Pilarová
authors.affiliation: NMR Spectroscopy Unit, Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: Ján
authors.initials: J
authors.lastname: Tarábek
authors.affiliation: Department of Parasitology, Charles University in Prague, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Tachezy
authors.affiliation: Department of Parasitology, Charles University in Prague, Prague, Czech Republic hrdy@cesnet.cz.
authors.forename: Ivan
authors.initials: I
authors.lastname: Hrdý
mesh_terms: D000595:Amino Acid Sequence; D000994:Antitrichomonal Agents / Q000494:pharmacology; D002384:Catalysis; D004351:Drug Resistance; D005288:Ferredoxins / Q000378:metabolism; D005420:Flavoproteins / Q000378:metabolism; D005800:Genes, Fungal; D006859:Hydrogen / Q000378:metabolism*; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D008795:Metronidazole / Q000737:chemistry / Q000494:pharmacology; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014246:Trichomonas vaginalis / Q000378:metabolism*
chemical_list: D000994:Antitrichomonal Agents; D005288:Ferredoxins; D005420:Flavoproteins; D007506:Iron-Sulfur Proteins; D009243:NAD; D008795:Metronidazole; D006859:Hydrogen