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Transglutaminase 2 inhibitors and their therapeutic role in disease states Siegel M; Khosla CPharmacol Ther 2007[Aug]; 115 (2): 232-45Transglutaminase 2 (TG2) is a multi-domain, multi-functional enzyme that post-translationally modifies proteins by catalyzing the formation of intermolecular isopeptide bonds between glutamine and lysine side-chains. It plays a role in diverse biological functions, including extracellular matrix formation, integrin-mediated signaling, and signal transduction involving 7-transmembrane receptors. While some of the roles of TG2 under normal physiological conditions remain obscure, the protein is believed to participate in the pathogenesis of several unrelated diseases, including celiac sprue, neurodegenerative diseases, and certain types of cancer. A variety of small molecule and peptidomimetic inhibitors of the TG2 active site have been identified. Here, we summarize the biochemistry, biology, pharmacology and medicinal chemistry of human TG2.|Celiac Disease/drug therapy/enzymology[MESH]|Enzyme Inhibitors/*pharmacology/therapeutic use[MESH]|GTP-Binding Proteins/*antagonists & inhibitors/chemistry/physiology[MESH]|Humans[MESH]|Neoplasms/drug therapy/enzymology[MESH]|Neurodegenerative Diseases/drug therapy/enzymology[MESH]|Protein Conformation[MESH]|Protein Glutamine gamma Glutamyltransferase 2[MESH]|Signal Transduction[MESH]|Transglutaminases/*antagonists & inhibitors/chemistry/physiology[MESH] |
