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International Journal of Molecular... Aug 2023Stabilization and reusability of enzyme transglutaminase (TGM) are important goals for the enzymatic process since immobilizing TGM plays an important role in different... (Review)
Review
Stabilization and reusability of enzyme transglutaminase (TGM) are important goals for the enzymatic process since immobilizing TGM plays an important role in different technologies and industries. TGM can be used in many applications. In the food industry, it plays a role as a protein-modifying enzyme, while, in biotechnology and pharmaceutical applications, it is used in mediated bioconjugation due to its extraordinary crosslinking ability. TGMs (EC 2.3.2.13) are enzymes that catalyze the formation of a covalent bond between a free amino group of protein-bound or peptide-bound lysine, which acts as an acyl acceptor, and the γ-carboxamide group of protein-bound or peptide-bound glutamine, which acts as an acyl donor. This results in the modification of proteins through either intramolecular or intermolecular crosslinking, which improves the use of the respective proteins significantly.
Topics: Transglutaminases; Proteins; Biotechnology; Peptides; Glutamine
PubMed: 37569776
DOI: 10.3390/ijms241512402 -
Fish & Shellfish Immunology Dec 2022In crustacean animals the hemocytes are key players in immunity and of crucial importance for the health of the animals. Hemocytes are mainly produced in the... (Review)
Review
In crustacean animals the hemocytes are key players in immunity and of crucial importance for the health of the animals. Hemocytes are mainly produced in the hematopoietic tissue and from there released into the circulation where they finally mature. In this review we summarize the latest findings about crustacean hemocyte formation. The role of the extracellular matrix and crosslinking enzyme transglutaminase is discussed. Moreover, important growth factors, transcriptional regulation and recent findings about inducers of hematopoiesis are covered. Finally, we discuss the use of different markers for classification of crustacean hemocytes.
Topics: Animals; Hematopoiesis; Hemocytes; Crustacea; Transglutaminases
PubMed: 36216230
DOI: 10.1016/j.fsi.2022.10.008 -
Aging May 2017
Topics: Aldehyde Oxidoreductases; GTP-Binding Proteins; Gene Expression Regulation, Neoplastic; Humans; Neoplastic Stem Cells; Protein Glutamine gamma Glutamyltransferase 2; Transglutaminases
PubMed: 28476022
DOI: 10.18632/aging.101236 -
Frontiers in Bioscience (Landmark... Mar 2017Mitochondria are the cell's power plant to satisfy the energy demands. However, dysfunctional mitochondria can cause overproduction of reactive oxygen species (ROS),... (Review)
Review
Mitochondria are the cell's power plant to satisfy the energy demands. However, dysfunctional mitochondria can cause overproduction of reactive oxygen species (ROS), oxidative stress, and alteration of calcium homeostasis, which are the hallmarks of mitochondrial diseases. Under prolong oxidative stress, repeated cytosolic calcium elevations even only transiently, can lead to activation of some enzymes. One calcium-activated enzyme with demonstrated pathophysiological important in mitochondrial disease is tissue transglutaminase (TG2). TG2 is known as a post-translational modification (PTM) enzyme that is induced by oxidative stress. Compared to other types of PTMs, the physiological significance of TG2 mediated PTM is just beginning to be understood. Once activated, TG2 can modulate transcription, inactivate metabolic enzymes, and cause aggregation of critical proteins. Recent data indicate that TG2's activity not only can modulate the assembly of respiratory chain complexes but can also modulate the transcription of critical genes including PGC-1alpha and cytochrome C that are important for function and biogenesis of mitochondria. Here, we summarize dysfunctional mitochondria in diseases such as in neurodegenerative disorders can modulate TG2's activity and function. TG2 is also important for normal function of mitochondria.
Topics: Alzheimer Disease; Animals; Autoimmunity; Epithelial-Mesenchymal Transition; GTP-Binding Proteins; Gene Expression Regulation, Enzymologic; Humans; Huntington Disease; Mitochondria; Neurodegenerative Diseases; Parkinson Disease; Protein Glutamine gamma Glutamyltransferase 2; Transglutaminases; Wound Healing
PubMed: 28199195
DOI: 10.2741/4536 -
Journal of Medicinal Chemistry Jul 2023Tissue transglutaminase (TG2) is a multifunctional enzyme involved in the cross-linking of extracellular matrix proteins, formation of complexes with fibronectin (FN)...
Tissue transglutaminase (TG2) is a multifunctional enzyme involved in the cross-linking of extracellular matrix proteins, formation of complexes with fibronectin (FN) and integrins, and GTP hydrolysis. TG2 is activated in several pathological conditions, including cancer. We recently described a novel series of ligands that bind to TG2 and inhibit its interaction with FN. Because TG2 acts via multiple mechanisms, we set out to pursue a targeted protein degradation strategy to abolish TG2's myriad functions. Here, we report the synthesis and characterization of a series of VHL-based degraders that reduce TG2 in ovarian cancer cells in a proteasome-dependent manner. Degradation of TG2 resulted in significantly reduced cancer cell adhesion and migration in scratch-wound and migration assays. These results strongly indicate that further development of more potent and efficient TG2 degraders could be a new strategy for reducing the dissemination of ovarian and other cancers.
Topics: Female; Humans; Protein Glutamine gamma Glutamyltransferase 2; Transglutaminases; Proteolysis Targeting Chimera; GTP-Binding Proteins; Cell Adhesion
PubMed: 37449845
DOI: 10.1021/acs.jmedchem.2c01859 -
Folia Microbiologica May 2014The extremely high costs of manufacturing transglutaminase from animal origin (EC 2.3.2.13) have prompted scientists to search for new sources of this enzyme.... (Review)
Review
The extremely high costs of manufacturing transglutaminase from animal origin (EC 2.3.2.13) have prompted scientists to search for new sources of this enzyme. Interdisciplinary efforts have been aimed at producing enzymes synthesised by microorganisms which may have a wider scope of use. Transglutaminase is an enzyme that catalyses the formation of isopeptide bonds between proteins. Its cross-linking property is widely used in various processes: to manufacture cheese and other dairy products, in meat processing, to produce edible films and to manufacture bakery products. Transglutaminase has considerable potential to improve the firmness, viscosity, elasticity and water-binding capacity of food products. In 1989, microbial transglutaminase was isolated from Streptoverticillium sp. Its characterisation indicated that this isoform could be extremely useful as a biotechnological tool in the food industry. Currently, enzymatic preparations are used in almost all industrial branches because of their wide variety and low costs associated with their biotechnical production processes. This paper presents an overview of the literature addressing the characteristics and applications of transglutaminase.
Topics: Animals; Biotechnology; Food Industry; Food Microbiology; Humans; Transglutaminases
PubMed: 24198201
DOI: 10.1007/s12223-013-0287-x -
BMB Reports Jan 2018Formation of toxic protein aggregates is a common feature and mainly contributes to the pathogenesis of neurodegenerative diseases (NDDs), which include amyotrophic... (Review)
Review
Formation of toxic protein aggregates is a common feature and mainly contributes to the pathogenesis of neurodegenerative diseases (NDDs), which include amyotrophic lateral sclerosis (ALS), Alzheimer's, Parkinson's, Huntington's, and prion diseases. The transglutaminase 2 (TG2) gene encodes a multifunctional enzyme, displaying four types of activity, such as transamidation, GTPase, protein disulfide isomerase, and protein kinase activities. Many studies demonstrated that the calcium-dependent transamidation activity of TG2 affects the formation of insoluble and toxic amyloid aggregates that mainly consisted of NDD-related proteins. So far, many important and NDD-related substrates of TG2 have been identified, including amlyoid-β, tau, α-synuclein, mutant huntingtin, and ALS-linked trans-activation response (TAR) DNA-binding protein 43. Recently, the formation of toxic inclusions mediated by several TG2 substrates were efficiently inhibited by TG2 inhibitors. Therefore, the development of highly specific TG2 inhibitors would be an important tool in alleviating the progression of TG2-related brain disorders. In this review, the authors discuss recent advances in TG2 biochemistry, several mechanisms of molecular regulation and pleotropic signaling functions, and the presumed role of TG2 in the progression of many NDDs. [BMB Reports 2018; 51(1): 5-13].
Topics: Animals; GTP-Binding Proteins; Humans; Neurodegenerative Diseases; Protein Aggregation, Pathological; Protein Glutamine gamma Glutamyltransferase 2; Transglutaminases
PubMed: 29187283
DOI: 10.5483/bmbrep.2018.51.1.227 -
Advanced Science (Weinheim,... Sep 2023Dermatitis herpetiformis (DH) is an inflammatory skin disorder often considered as an extra intestinal manifestation of celiac disease (CeD). Hallmarks of CeD and DH are...
Dermatitis herpetiformis (DH) is an inflammatory skin disorder often considered as an extra intestinal manifestation of celiac disease (CeD). Hallmarks of CeD and DH are auto-antibodies to transglutaminase 2 (TG2) and transglutaminase 3 (TG3), respectively. DH patients have auto-antibodies reactive with both transglutaminase enzymes. Here it is reported that in DH both gut plasma cells and serum auto-antibodies are specific for either TG2 or TG3 with no TG2-TG3 cross reactivity. By generating monoclonal antibodies from TG3-specific duodenal plasma cells of DH patients, three conformational epitope groups are defined. Both TG2-specific and TG3-specific gut plasma cells have few immunoglobulin (Ig) mutations, and the two transglutaminase-reactive populations show distinct selection of certain heavy and light chain V-genes. Mass spectrometry analysis of TG3-specific serum IgA corroborates preferential usage of IGHV2-5 in combination with IGKV4-1. Collectively, these results demonstrate parallel induction of anti-TG2 and anti-TG3 auto-antibody responses involving separate B-cell populations in DH patients.
Topics: Humans; Celiac Disease; Dermatitis Herpetiformis; Immunoglobulin A; Plasma Cells; Protein Glutamine gamma Glutamyltransferase 2; Transglutaminases
PubMed: 37424036
DOI: 10.1002/advs.202300401 -
Analytical Biochemistry Feb 2020Transglutaminase 2 (TG2) is a ubiquitous but enigmatic mammalian protein to which a number of biological functions have been ascribed but not definitively proven. As a... (Review)
Review
Transglutaminase 2 (TG2) is a ubiquitous but enigmatic mammalian protein to which a number of biological functions have been ascribed but not definitively proven. As a member of the transglutaminase family, TG2 can catalyze deamidation or alternatively transamidation of selected Gln residues in proteins and peptides. It is also known to harbor other enzymatic properties, including protein disulfide isomerase, GTP-dependent signal transduction, and ATP dependent protein kinase activity. Given its multifunctional chemistry, it is unsurprising that a long list of proteins from the mammalian proteome have been identified as substrates and/or binding partners; however, the biological relevance of none of these protein-protein interactions has been clarified as yet. Remarkably, the most definitive insights into the biology of TG2 stem from its pathophysiological role in gluten peptide deamidation in celiac disease. Meanwhile our understanding of TG2 chemistry has been leveraged to engineer a spectrum of inhibitors and other molecular probes of TG2 biology in vivo. This review summarizes our current knowledge of the enzymology and regulation of human TG2 with a focus on its physiological substrates as well as tool molecules whose engineering was inspired by their identities.
Topics: Animals; Biocatalysis; Celiac Disease; GTP-Binding Proteins; Glutens; Humans; Ligands; Peptides; Protein Binding; Protein Glutamine gamma Glutamyltransferase 2; Transglutaminases
PubMed: 31874171
DOI: 10.1016/j.ab.2019.113560 -
Cells Aug 2020Transglutaminases (TGMs) contribute to the formation of rigid, insoluble macromolecular complexes, which are essential for the epidermis and hair follicles to perform... (Review)
Review
Transglutaminases (TGMs) contribute to the formation of rigid, insoluble macromolecular complexes, which are essential for the epidermis and hair follicles to perform protective and barrier functions against the environment. During differentiation, epidermal keratinocytes undergo structural alterations being transformed into cornified cells, which constitute a highly tough outermost layer of the epidermis, the stratum corneum. Similar processes occur during the hardening of the hair follicle and the hair shaft, which is provided by the enzymatic cross-linking of the structural proteins and keratin intermediate filaments. TGM3, also known as epidermal TGM, is one of the pivotal enzymes responsible for the formation of protein polymers in the epidermis and the hair follicle. Numerous studies have shown that TGM3 is extensively involved in epidermal and hair follicle physiology and pathology. However, the roles of TGM3, its substrates, and its importance for the integument system are not fully understood. Here, we summarize the main advances that have recently been achieved in TGM3 analyses in skin and hair follicle biology and also in understanding the functional role of TGM3 in human tumor pathology as well as the reliability of its prognostic clinical usage as a cancer diagnosis biomarker. This review also focuses on human and murine hair follicle abnormalities connected with TGM3 mutations.
Topics: Animals; Cell Differentiation; Disease Models, Animal; Epithelial Cells; Humans; Mice; Neoplasms; Transglutaminases
PubMed: 32872587
DOI: 10.3390/cells9091996