Thioredoxin glutathione reductase (TGR) is one of the promising novel targets to combat schistosomiasis. Our collaborator Dr. David Williams laboratory have generated compelling evidence that schistosome redox defenses are limited, that they can be disrupted pharmacologically by inhibiting TGR, and that their disruption leads to worm death in vitro and in vivo (Prast-Nielsen, Huang et al. 2011, Huang, Rigouin et al. 2012, Williams, Bonilla et al. 2013).

The pioneering structural studies by Dr. Francesco Angelucci unveiled for the first time the unique domain architecture of a TGR enzyme (PDB:2V6O). TGR is a “W”-shaped homodimer formed by the fusion of a TrxR domain to a Grx domain. Further extensive biochemical analyses of TGR combined with 3D structures of TGR complexes with various substrates, covalent inhibitors (for example auranofin), and in different redox states (Angelucci, Miele et al. 2008, Angelucci, Sayed et al. 2009, Angelucci, Dimastrogiovanni et al. 2010, Huang, Day et al. 2011, Silvestri, Lyu et al. 2018, Silvestri, Lyu et al. 2019) allowed Angelucci and Williams laboratories to define in detail the catalytic mechanisms of TGR.