transglutaminasemediated

Transglutaminasemediated describes biological processes driven by the transglutaminase family of enzymes. These enzymes catalyze the formation of covalent cross-links between proteins by creating isopeptide bonds between the γ-carboxamide group of a glutamine residue and the ε-amino group of a lysine residue. In some cases, transglutaminases can also catalyze deamidation of glutamine to glutamic acid, particularly in calcium-rich environments. The reactions require calcium and can be influenced by factors such as redox state and, for certain family members, nucleotide binding.

The human transglutaminase family includes several members, with tissue transglutaminase (TG2) being widely expressed and multifunctional. Coagulation factor XIIIa is another well-known transglutaminase that cross-links fibrin during clot formation. Additional members, such as TG1 through TG7, display tissue-specific distributions and substrate preferences, contributing to diverse physiological roles.

Physiological roles of transglutaminase-mediated processes include stabilization of the extracellular matrix and the cornified envelope in skin, cross-linking of fibrin in blood clots, and involvement in wound healing and tissue remodeling. In food science, transglutaminases are used to improve texture by cross-linking dietary proteins, such as those in meat products or dairy.

Pathological relevance centers on dysregulated transglutaminase activity. In celiac disease, TG2 modifies gluten peptides through deamidation and cross-linking, contributing to autoantigen formation and inflammation. Aberrant TG activity has also been implicated in fibrosis and certain cancers, prompting ongoing research into inhibitors and therapeutic strategies.

Applications and research avenues include designing TG inhibitors for fibrotic diseases, utilizing transglutaminase-catalyzed cross-linking to create biomaterials and hydrogels, and employing TGs for bioconjugation and protein engineering.