Structural Biochemistry/Enzyme Catalytic Mechanism/Glutathione Reductase

General InformationEdit

Oxidation-reduction enzyme

Uses coenzymes NADP+/NADPH and FAD/FADH2

In humans, this is a dimer of 478-amino acid subunits linked by disulfide bond

Two-stage reaction

1st stage: E + NADPH + H+ EH2 + NADP+

Oxidized E binds NADPH, immediately reduces FAD, producing NADP+.

E contains redox-active disulfide bond (Cys58-Cys63), which has accepted an electron pair in EH2 to form a dithiol (one S- is in a charge transfer complex with FADH-)

2nd stage: EH2 + GSSG E + 2GSH

GSSG binds to EH2

Cys58 nucleophile attacks one S of GSSG yielding mixed disulfide, promoted by His467' acting as general base

One GSH is kicked-off by protonation by His467' (general acid)

Cys63 nucleophile attacks Cys58 to form redox-active disulfide, kicking off second GSH