A5063860305- Blood properties and coagulation
- Erythrocyte Function and Pathophysiology
- Rheology and Fluid Dynamics Studies
- Skin and Cellular Biology Research
- Protein purification and stability
- Adipokines, Inflammation, and Metabolic Diseases
- Erythropoietin and Anemia Treatment
- Transgenic Plants and Applications
University of Ottawa
2021-2024
Our investigation of small, irreversible TG2 inhibitors identifies key components that confer enhanced efficiency, and reveals potential discrepancies in the use current crystallographic models for predicting inhibitor potency.
Transglutaminase 2 (TG2) performs many functions both under physiological and pathological conditions. In cancer, its expression is associated with aggressiveness, propensity to epithelial-mesenchymal transition, metastasis. Since TG2 key outside inside the cell, using inhibitors different membrane permeability we analyzed changes in transcriptome induced two triple-negative cell lines (MDA-MB-436 MDA-MB-231) aggressive features. By characterizing pathways gene networks, were able define...
Abstract Type 2 transglutaminase (TG2) functions as an important cancer cell survival protein in a range of cancers including epidermal squamous carcinoma. TG2 exists open and closed conformations each which has distinct mutually exclusive activity. The conformation GTP‐binding/GTPase activity while the transamidase to catalyze protein‐protein crosslinking. is required for maintenance aggressive phenotype. Thus, identifying agents that convert from inactive prevention/treatment strategy....
Transglutaminase 2 (TG2) is a multifunctional enzyme primarily responsible for crosslinking proteins. Ubiquitously expressed in humans, TG2 can act either as transamidase by two substrates through formation of an Nε(ɣ-glutaminyl)lysine bond or intracellular G-protein. These discrete roles are tightly regulated both allosteric and environmental stimuli associated with dramatic changes the conformation enzyme. The pleiotropic nature multi-faceted activities have resulted being implicated...
Transglutaminases (TGases) are a family of calcium-dependent enzymes primarily known for their ability to cross-link proteins. Transglutaminase 2 (TG2) is one isozyme in this whose role multifaceted. TG2 can act not only as typical transamidase through its catalytic core but also G-protein via GTP binding site. These two discrete activities tightly regulated by both environmental stimuli and redox reactions. Ubiquitously expressed humans, has been implicated numerous disease pathologies that...
Transglutaminase 2 (TG2), also referred to as tissue transglutaminase, plays crucial roles in both protein crosslinking and cell signalling. It is capable of catalysing transamidation acting a G-protein, these activities being conformation-dependent, mutually exclusive, tightly regulated. The dysregulation has been implicated numerous pathologies. TG2 expressed ubiquitously humans localized intracellularly extracellularly. Targeted therapies have developed but faced hurdles including...
Factor XIIIa (FXIIIa) is a transglutaminase of major therapeutic interest for the development anticoagulants due to its essential role in blood coagulation cascade. While numerous FXIIIa inhibitors have been reported, they failed reach clinical evaluation their lack metabolic stability and low selectivity over 2 (TG2). Furthermore, chemical tools available study activity localization are extremely limited. To combat these shortcomings, we designed, synthesised, evaluated library 21 novel...
Since the multifunctionality of transglutaminase 2 (TG2) includes extra- and intracellular functions, we investigated effects administration TG2 inhibitors in three breast cancer cell lines, MDA-MB-231, MDA-MB-436 MDA-MB-468, which are representative different triple-negative phenotypes, using a patch-clamp technique. The first line has highly voltage-dependent membrane current, is low second almost absent third one. While applying voltage protocol to responsive single cells, injection...