Abstract
The activity of human transglutaminase 2 (TG2), which forms protein cross-links between glutamine and lysine residues, is controlled by an allosteric disulfide bond. However, the mechanism by which this bond is formed, like many systems regulated by oxidative cysteine modifications, was not clear. A new study from Khosla and colleagues shows that TG2 is oxidatively inactivated by the protein disulfide isomerase ERp57, providing the first example of a defined and reversible protein-controlled redox switch and pointing to new strategies to inhibit undesirable TG2 activity in pathological states.