Transglutaminases catalyze the acyl-transfer reaction between a γ-carboxamide group of glutamine and the ε-amino group of lysine, which results in the formation of isopeptide bonds. Human transglutaminases possess a catalytic triad and the reaction proceeds via a reactive intermediate linked to the nucleophilic cysteine of the enzyme. The mechanism is similar to the proteolysis reaction catalyzed by thiol proteases that posses the same catalytic triad. It turned out that transglutaminases are using a similar structural architecture as papain-like thiol proteases and obviously even have an evolutionary relationship.
Also biology and physiology are closely related. E.g. the transglutaminasecoagulation factor XIIIa cross-links fibrin and therefore plays an important role in blood clot formation. The serine protease thrombin (T056) activates factor XIII cleaving the activation peptide. Subsequently, plasmin (P012) degrades the fibrin clot. Therefore proteases are important tools in transglutaminase research.