Nejvíce citovaný článek - PubMed ID 16304169
Alternative pathway of metronidazole activation in Trichomonas vaginalis hydrogenosomes
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
- antitrichomonádové látky farmakologie MeSH
- ferredoxiny metabolismus MeSH
- flavoproteiny metabolismus MeSH
- geny hub MeSH
- katalýza MeSH
- léková rezistence MeSH
- metronidazol chemie farmakologie MeSH
- molekulární sekvence - údaje MeSH
- NAD metabolismus MeSH
- proteiny obsahující železo a síru metabolismus MeSH
- sekvence aminokyselin MeSH
- subcelulární frakce účinky léků metabolismus MeSH
- Trichomonas vaginalis metabolismus MeSH
- vodík metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antitrichomonádové látky MeSH
- ferredoxiny MeSH
- flavoproteiny MeSH
- metronidazol MeSH
- NAD MeSH
- proteiny obsahující železo a síru MeSH
- vodík 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
- ferredoxiny chemie genetika izolace a purifikace metabolismus MeSH
- flavinmononukleotid metabolismus MeSH
- kyslík metabolismus MeSH
- molekulární sekvence - údaje MeSH
- organely chemie enzymologie genetika MeSH
- oxidoreduktasy chemie genetika izolace a purifikace metabolismus MeSH
- protozoální proteiny chemie genetika izolace a purifikace metabolismus MeSH
- sekvence aminokyselin MeSH
- substrátová specifita MeSH
- Trichomonas vaginalis chemie enzymologie genetika MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ferredoxiny MeSH
- flavinmononukleotid MeSH
- kyslík MeSH
- oxidoreduktasy MeSH
- protozoální proteiny MeSH