Physio-pathological roles of transglutaminase-catalyzed reactions

Figure 1 Transglutaminase (TG)-catalyzed reactions. R: Monoamines, polyamines. Examples of TG-catalyzed reactions: A: Acyl transfer between the γ-carboxamide group of a protein/polypeptide glutaminyl residue and the epsilon-amino group of a protein/polypeptide lysyl residue; B: Attachment of a polyamine to the carboxamide group of a glutaminyl residue; C: Deamidation of the γ-carboxamide group of a protein/polypeptide glutaminyl residue.

Figure 2 Schematic representation of a two step transglutaminase reaction. Step 1: In the presence of Ca²⁺, the active-site cysteine residue reacts with the γ-carboxamide group of an incoming glutaminyl residue of a protein/peptide substrate to yield a thioacyl-enzyme intermediate and ammonia; Step 2: The thioacyl-enzyme intermediate reacts with a nucleophilic primary amine substrate, resulting in the covalent attachment of the amine-containing donor to the substrate glutaminyl acceptor and regeneration of the cysteinyl residue at the active site. If the primary amine is donated by the epsilon-amino group of a lysyl residue in a protein/polypeptide, a N^ε-(γ-L-glutamyl)-L-lysine (GGEL) isopeptide bond is formed.

Figure 3 Possible mechanisms responsible for protein aggregate formation catalyzed by transglutaminase.

Figure 4 Chemical structure of cystamine.