Thioredoxins, which are antioxidant enzymes that are ubiquitous in living organisms, catalyze the reduction of disulfide bonds. An international team headed by Julio M. Fernández at Columbia University has taken a closer look at the dynamics of thioredoxin catalysis with the aid of single-molecule force-clamp spectroscopy, which is a variant of atomic force microscopy (Nature 2007, 450, 124). The group stretched single strands of a short substrate protein, straightening out the molecule's tertiary structure and baring disulfide bonds that normally are hidden within. The researchers then bathed the exposed disulfide bonds in a solution containing thioredoxin enzymes and studied the dependence of the rate of bond reduction on mechanical force pulses. They discovered two disulfide bond conformations that allow the enzyme to facilitate the reduction. In one case, a disulfide bond reorients and shortens the substrate; in the other case, the disulfide bond is elongated. The findings add to the notion that substrate geometry is important for disulfide reduction, according to the authors.