Dermal Dendrocytes
Brian J. Nickoloff in Dermal Immune System, 2019
Transglutaminases catalyze posttranslational modifications of extracellular proteins to form bonds which are covalent, stable, and resistant to proteolysis.17 Factor XIIIa is one of four well-characterized transglutaminases.14 The others are tissue transglutaminase (TGc), keratinocyte transglutaminase (TGk), and epidermal transglutaminase (TGe). The distribution of TGc in normal human skin has not been well characterized but it is probably found in endothelial cells and might occur in some dermal dendritic cells as well. TGc has an affinity for fibronectin, fibrin, and type I collagen. Without speculation about the possible origin and role of dermal TGc in hemostasis and wound healing, it is already known that factor XIIIa cross-links plasma fibronectin as it is being assembled into the extracellular matrix of cultured skin fibroblasts.18
Manufacture and Applications of Gelatin Nanoparticles: A Practical Approach
Andreia Ascenso, Sandra Simões, Helena Ribeiro in Carrier-Mediated Dermal Delivery, 2017
Won et al. [15] used human recombinant gelatin as raw material for the nanoparticle formation and genipin as the cross- link agent, less toxic than glutaraldehyde. The obtained nanoparticles were considered stable (after 6 months storage) and with 250 nm diameter. Fuchs et al. [16] evaluated the effect of another possible cross-link agent. These authors successfully used transglutaminase, an enzyme isolated from Escherichia coli. However, the reaction conditions were slightly different from the conventional desolvation protocol. In this method, the final nanoparticles suspension was diluted in purified water in order to obtain an adequate medium for the enzyme. Qazvini et al. [17] also assessed another non-toxic cross-link agent for gelatin. A mixture of carbodiimide and N-hydroxysuccinimide (CDI/NHS) in water was used, and its cross-link effect was compared with glutaraldehyde (GA). CDI/NHS nanoparticles were much smaller than the GA ones. Paracetamol encapsulation efficiency was found to be 10% and 27% in GA and CDI/NHS, respectively.
Biochemical Parameters: Childhood Diarrhea and Malabsorption Syndrome
Anil Gupta in Biochemical Parameters and the Nutritional Status of Children, 2020
Tissue transglutaminase is a calcium cofactor dependent enzyme that catalyzes the post-translational modification of polypeptides. It results in the formation of an isopeptide bond between the γ-carboxamide group of glutaminyl residue and ε amino group of lysyl residue, which are present either in similar or different polypeptides (Folk and Finlayson 1977). Tissue transglutaminase enzyme is widely distributed in the body tissues. The tissue transglutaminase enzyme is concerned with the cross linking of peptides in the glutamine residue.
Transglutaminase 2 mediates lung inflammation and remodeling by transforming growth factor beta 1 via alveolar macrophage modulation
Published in Experimental Lung Research, 2021
Young Chan Kim, Jeonghyeon Kim, Subin Kim, Boram Bae, Ruth Lee Kim, Eui-Man Jeong, Sang-Heon Cho, Hye-Ryun Kang
Transglutaminase is a calcium-dependent enzyme that catalyzes protein cross-linking, polyamination, or deamidation at selective glutamine residues.11 Among the several types of TGs with a high degree of sequence similarity,12 TG2 is the enzyme most widely expressed in numerous cell types. It is localized to multiple cell compartments, including the cytosol, mitochondria, and cell surface.13 Since TGF-β1 is synthesized in an inactive form, activation of latent TGF-β1 is required to initiate TGF-β1 signaling.14 TG2 cross-links the N-terminal region of latent TGF-β binding protein 1 to ECM proteins,15 whereas TGF-β1 increases membrane-associated extracellular TG2 expression in idiopathic pulmonary fibrosis. In mice, TG2 deletion suppresses pulmonary fibrosis after bleomycin challenge, which normally induces the release of the active form of TGF-β1 by alveolar macrophages.16
Antibody-drug conjugates: Design and development for therapy and imaging in and beyond cancer, LabEx MAbImprove industrial workshop, July 27–28, 2017, Tours, France
Published in mAbs, 2018
Camille Martin, Claire Kizlik-Masson, André Pèlegrin, Hervé Watier, Marie-Claude Viaud-Massuard, Nicolas Joubert
The session began with Dr. Saïd El Alaoui (Covalab, Villeurbanne, France) who presented a new bacterial transglutaminase Q-tag substrate for site-specific ADC conjugation.23 Transglutaminase catalyzes the formation of a covalent bond between a free amino group and the carboxamide group of a protein or peptide glutamine. The best microbial transglutaminase (TGm) substrates were identified by screening different glutamine-containing peptides. These sequences were then C-terminally fused with each heavy chain of an anti-HER2 antibody, and enzymatic conjugation was performed with an amine-containing payload: AlexaFluor®488-cadaverine. No difference in ADC antigen binding was observed by enzyme-linked immunosorbent assay (ELISA) and Biacore. With the anti-HER2 antibody, the conjugation was better with: (1) the optimum glutamine donor substrate (Q-tag1) than with known peptide substrates like LLQG, because of the substrate enhanced affinity, and (2) a mutated antibody presenting lysine depletion, which avoids non-specific conjugation. Conjugations made in this way are homogeneous and reproducible.
Identification and characterization of protein cross-links induced by oxidative reactions
Published in Expert Review of Proteomics, 2018
Per Hägglund, Michele Mariotti, Michael J. Davies
Transglutaminase enzymes catalyze the formation of an amide bond (often termed isopeptide) between an amine function (e.g. the Lys side-chain) and an acyl group of another amino acid (typically glutamine). These reactions are important in a number of biological and industrial processes including the blood coagulation cascade [124], neurodegenerative conditions [10,125], ubiquitination of proteins (where they are used as a signal for proteasomal degradation, but can also be used a marker for protein trafficking and to alter protein structure and interactions [126]), the generation of new food matrices (e.g. as a “glue” for meat and fish products), and improvements in food textures (e.g. in ham) [8,9]. An absence of members of the transglutaminase enzyme family has been linked with a number of human pathologies, indicating its importance in generating correct biological structures [127]. Ubiquitination occurs via the action of a family of enzymes (activating, conjugating, and ligase species) and can generate not only classical Lys-Gln linkages, but also thioester bonds from Cys residues, ester bonds from Ser and Thr, and also classical peptide bonds via the N-terminal amine [126].