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. Author manuscript; available in PMC: 2021 Mar 13.
Published in final edited form as: ACS Infect Dis. 2020 Jan 24;6(3):393–405. doi: 10.1021/acsinfecdis.9b00354

Scheme 1. The catalytic cycle of TGR.

Scheme 1.

The reaction scheme was drawn following the proposed mechanism of SmTGR.1617 When NADPH binds to dimeric oxidized TGR (A), FAD is reduced and then donates electrons to the proximal C154-C159 couple (B). The electrons are then transferred to the C596’-U597’ couple on the C-terminus of the other subunit (C). The reduced C-terminus transfers electrons to C28-C31 couple of Grx domain of the original subunit and additional NADPH reduces FAD and electrons are transferred to the proximal C154-C159 couple (D). The electrons are then transferred to the C596’-U597’ couple (E). This enzyme form can reduce both oxidized Trx (or DTNB) and GSSG.