Redox properties of the oxygen-detoxifying flavodiiron protein from the human parasite Giardia intestinalis

Abstract

Flavodiiron proteins (FDPs) are enzymes identified in prokaryotes and a few pathogenic protozoa, which protect microorganisms by reducing O 2 to H 2O and/or NO to N 2O. Unlike most prokaryotic FDPs, the protozoan enzymes from the human pathogens Giardia intestinalis and Trichomonas vaginalis are selective towards O 2. UV/vis and EPR spectroscopy showed that, differently from the NO-consuming bacterial FDPs, the Giardia FDP contains an FMN with reduction potentials for the formation of the single and the two-electron reduced forms very close to each other ( E 1 = −66 ± 15 mV and E 2 = −83 ± 15 mV), a condition favoring destabilization of the semiquinone radical. Giardia FDP contains also a non-heme diiron site with significantly up-shifted reduction potentials ( E 1 = +163 ± 20 mV and E 2 = +2 ± 20 mV). These properties are common to the Trichomonas hydrogenosomal FDP, and likely reflect yet undetermined subtle structural differences in the protozoan FDPs, accounting for their marked O 2 specificity.