Fig. 1: Structural differences between enzymatically active and inactive Grx.
a Enzymatically active glutaredoxins (Grx) use reduced glutathione (GSH) as an electron donor for the reduction of high- and low-molecular weight glutathione disulfide substrates (GSSR) or non-glutathione disulfide substrates (RSSR’) as highlighted in the left half of the panel. The Grx-catalyzed reduction of GSSR by GSH is separated into an oxidative and reductive half-reaction as highlighted by the two predicted transition states and glutathione interaction sites in the schematic representations in the right half of the panel. b Structure of enzymatically active Grx. A schematic representation of four specialized protein areas, NMR solution structures of the glutathionylated C14S mutant of enzymatically active EcGrx3 (PDB entry 3GRX), and a model of glutathionylated ScGrx7 are shown from left to right. Please note that the glutathione moiety as well as the conserved active-site cysteine (Ca) and lysine (Ka) residue adopt several alternative positions in the NMR structures. c Structure of enzymatically inactive Grx. A schematic representation of four specialized protein areas, NMR solution structures of enzymatically inactive EcGrx4 (PDB entry 1YKA), and the crystal structure of EcGrx4 in complex with an iron–sulfur cluster (PDB entry 2WCI, one EcGrx4 subunit and one GS− ligand were omitted for clarity) are shown from left to right. Please note the conformational change of the elongated loop and the repositioning of the active-site cysteine and lysine residue upon iron–sulfur cluster binding. d Sequence alignment of glutaredoxin isoforms and comparison with other proteins of the thioredoxin superfamily from A. thaliana (At), S. cerevisiae (Sc), Homo sapiens (Hs), E. coli (Ec), P. falciparum (Pf), and C. glutamicum (Cg). Established as well as potential glutathione-interacting residues r1–8 are highlighted.
