FIGURE 1.

Electron transfer in and out of the TR domain of SmTGR. The reaction scheme has been drawn following the experimental evidence reported in this work and elsewhere (18). When NADPH binds to the oxidized state of the enzyme (Structure 1), electrons are transferred from the nicotinamide ring to the FAD; reduced FADH₂ donates electrons to the Cys¹⁵⁴–Cys¹⁵⁹ couple (in red) that is close to the isoalloxazine ring of the cofactor (as observed in Structure 2), and finally electrons reach the Cys⁵⁹⁶–Sec⁵⁹⁷ redox couple on the C-terminal segment of the other subunit (in blue, as observed in Structure 3). The C terminus acts as a flexible arm, which might donate electrons either internally to the Cys²⁸–Cys³¹ redox active couple on the oxidized Grx domain (in green) or externally to various oxidized substrates such as SmTrx (in dark gray).