Regulation of the activities of the mammalian transglutaminase family of enzymes

Authors

  • Cornelius Klöck,

    1. Department of Chemistry, Stanford University, Stanford, California 94305
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  • Chaitan Khosla

    Corresponding author
    1. Department of Chemistry, Stanford University, Stanford, California 94305
    2. Department of Chemical Engineering, Stanford University, Stanford, California 94305
    • Departments of Chemistry and Chemical Engineering, Stanford University, Stanford, CA 94305
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Abstract

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.

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