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.

• MeSH
• Antitrichomonal Agents pharmacology   MeSH
• Ferredoxins metabolism   MeSH
• Flavoproteins metabolism   MeSH
• Genes, Fungal MeSH
• Catalysis MeSH
• Drug Resistance MeSH
• Metronidazole chemistry   pharmacology   MeSH
• Molecular Sequence Data MeSH
• NAD metabolism   MeSH
• Iron-Sulfur Proteins metabolism   MeSH
• Amino Acid Sequence MeSH
• Subcellular Fractions drug effects   metabolism   MeSH
• Trichomonas vaginalis metabolism   MeSH
• Hydrogen metabolism   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Antitrichomonal Agents MeSH
• Ferredoxins MeSH
• Flavoproteins MeSH
• Metronidazole MeSH
• NAD MeSH
• Iron-Sulfur Proteins MeSH
• Hydrogen MeSH

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.

• MeSH
• Ferredoxins chemistry   genetics   isolation & purification   metabolism   MeSH
• Flavin Mononucleotide metabolism   MeSH
• Oxygen metabolism   MeSH
• Molecular Sequence Data MeSH
• Organelles chemistry   enzymology   genetics   MeSH
• Oxidoreductases chemistry   genetics   isolation & purification   metabolism   MeSH
• Protozoan Proteins chemistry   genetics   isolation & purification   metabolism   MeSH
• Amino Acid Sequence MeSH
• Substrate Specificity MeSH
• Trichomonas vaginalis chemistry   enzymology   genetics   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Ferredoxins MeSH
• Flavin Mononucleotide MeSH
• Oxygen MeSH
• Oxidoreductases MeSH
• Protozoan Proteins MeSH