Interdomain electron transfer in flavohaemoglobin from Candida norvegensis with antibiotic azole compounds

Flavohaemoglobins (FlavoHbs) function as nitric oxide dioxygenases, oxidizing nitric oxide with nitrite and shuttling electrons from NAD(P)H via FAD and O-2. Here, using pulse radiolysis, we investigate intramolecular electron transfer between FAD and haem b in FlavoHbs. We found that reduction of FlavoHb with hydrated electrons proceeded via two phases: an initial fast phase and a second slower process. Absorbance measured at 600 nm revealed fast flavin reduction followed by a slower decrease corresponding to reoxidation of FAD. The slower process was partially lost in FlavoHbs lacking FAD. These results suggest that the slower phase is attributable to intramolecular electron transfer from FAD to the haem iron. The rate constant in the absence of azole compound (3.3 x 10(3) s(-1)) was accelerated similar to 10-fold (2.7 x 10(4) s(-1)) by the binding of econazole, reflecting a conformational change in the open-to-closed transition.

Automated summary

In this study, intramolecular electron transfer between FAD and haem b in FlavoHbs was investigated using pulse radiolysis. The results showed that the reduction of FlavoHb proceeded in two phases, with the slower phase attributed to intramolecular electron transfer from FAD to the haem iron. Additionally, the binding of azole compounds accelerated this process, indicating a conformational change.