Regulation of the activities of the mammalian transglutaminase family of enzymes

• Published in: Protein science Vol. 21; no. 12; pp. 1781 - 1791
• Main Authors: Klöck, Cornelius, Khosla, Chaitan
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.12.2012; Wiley Subscription Services, Inc
• Subjects: Allosteric Regulation - drug effects; allostery; Animals; disulfide redox switch; Enzymes; Gene expression; human mutations; Humans; Models, Molecular; Mutation; post‐translational modification; Protein Conformation; Protein Processing, Post-Translational; Proteins; Reviews; transglutaminase; Transglutaminases - antagonists & inhibitors; Transglutaminases - chemistry; Transglutaminases - genetics; Transglutaminases - metabolism
• ISSN: 0961-8368; 1469-896X
• DOI: 10.1002/pro.2162

Mammalian transglutaminases catalyze post‐translational modifications of glutamine residues on proteins and peptides through transamidation or deamidation reactions. Their catalytic mechanism resembles that of cysteine proteases. In virtually every case, their enzymatic activity is modulated by elaborate strategies including controlled gene expression, allostery, covalent modification, and proteolysis. In this review, we focus on our current knowledge of post‐translational regulation of transglutaminase activity by physiological as well as synthetic allosteric agents. Our discussion will primarily focus on transglutaminase 2, but will also compare and contrast its regulation with Factor XIIIa as well as transglutaminases 1 and 3. Potential structure–function relationships of known mutations in human transglutaminases are analyzed.