Mechanism and implication of warfarin tight-binding inhibition. (A) Difference between GSH and DTT. (Top) GSH maintains the native conformation of VKORC1 required for the tight binding of warfarin. This conformation is stabilized by a disulfide bond in the partially oxidized state.¹⁸  (Bottom) DTT fully reduces VKORC1, generating a conformation hindering warfarin binding. (B) Stoichiometric binding of warfarin explains the change of therapeutic window (orange and blue shades). The SNP inhibition curves are from Figure 1B. The dashed line indicates VKORC1 activity inhibited to the same level for the 2 SNPs.