scholarly journals Transglutaminases: Nature’s biological glues

2002 ◽  
Vol 368 (2) ◽  
pp. 377-396 ◽  
Author(s):  
Martin GRIFFIN ◽  
Rita CASADIO ◽  
Carlo M. BERGAMINI
Keyword(s):  
Blood Clotting ◽  
High Molecular Mass ◽  
Primary Amines ◽  
Commercial Sector ◽  
Biotechnological Applications ◽  
Post Translational Modification ◽  
Important Group ◽  
Isopeptide Bonds ◽  
Biological Glues

Transglutaminases (Tgases) are a widely distributed group of enzymes that catalyse the post-translational modification of proteins by the formation of isopeptide bonds. This occurs either through protein cross-linking via ∊-(γ-glutamyl)lysine bonds or through incorporation of primary amines at selected peptide-bound glutamine residues. The cross-linked products, often of high molecular mass, are highly resistant to mechanical challenge and proteolytic degradation, and their accumulation is found in a number of tissues and processes where such properties are important, including skin, hair, blood clotting and wound healing. However, deregulation of enzyme activity generally associated with major disruptions in cellular homoeostatic mechanisms has resulted in these enzymes contributing to a number of human diseases, including chronic neurodegeneration, neoplastic diseases, autoimmune diseases, diseases involving progressive tissue fibrosis and diseases related to the epidermis of the skin. In the present review we detail the structural and regulatory features important in mammalian Tgases, with particular focus on the ubiquitous type 2 tissue enzyme. Physiological roles and substrates are discussed with a view to increasing and understanding the pathogenesis of the diseases associated with transglutaminases. Moreover the ability of these enzymes to modify proteins and act as biological glues has not gone unnoticed by the commercial sector. As a consequence, we have included some of the present and future biotechnological applications of this increasingly important group of enzymes.

scholarly journals Biocatalysis by Transglutaminases: A Review of Biotechnological Applications

Micromachines ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 562 ◽  
Author(s):  
Maria Savoca ◽  
Elisa Tonoli ◽  
Adeola Atobatele ◽  
Elisabetta Verderio
Keyword(s):  
Nutritive Value ◽  
Large Family ◽  
Catalytic Triad ◽  
Matrix Proteins ◽  
Primary Amines ◽  
Biotechnological Applications ◽  
Post Translational Modification ◽  
The Past ◽  
Lysine Residues ◽  
Isopeptide Bonds

The biocatalytic activity of transglutaminases (TGs) leads to the synthesis of new covalent isopeptide bonds (crosslinks) between peptide-bound glutamine and lysine residues, but also the transamidation of primary amines to glutamine residues, which ultimately can result into protein polymerisation. Operating with a cysteine/histidine/aspartic acid (Cys/His/Asp) catalytic triad, TGs induce the post-translational modification of proteins at both physiological and pathological conditions (e.g., accumulation of matrices in tissue fibrosis). Because of the disparate biotechnological applications, this large family of protein-remodelling enzymes have stimulated an escalation of interest. In the past 50 years, both mammalian and microbial TGs polymerising activity has been exploited in the food industry for the improvement of aliments’ quality, texture, and nutritive value, other than to enhance the food appearance and increased marketability. At the same time, the ability of TGs to crosslink extracellular matrix proteins, like collagen, as well as synthetic biopolymers, has led to multiple applications in biomedicine, such as the production of biocompatible scaffolds and hydrogels for tissue engineering and drug delivery, or DNA-protein bio-conjugation and antibody functionalisation. Here, we summarise the most recent advances in the field, focusing on the utilisation of TGs-mediated protein multimerisation in biotechnological and bioengineering applications.

scholarly journals Solventless and Metal-Free Synthesis of High-Molecular-Mass Polyaminoboranes from Diisopropylaminoborane and Primary Amines

2018 ◽  
Vol 130 (6) ◽  
pp. 1535-1538 ◽  
Author(s):  
Carlos Antonio De Albuquerque Pinheiro ◽  
Claire Roiland ◽  
Philippe Jehan ◽  
Gilles Alcaraz
Keyword(s):  
Molecular Mass ◽  
High Molecular Mass ◽  
Primary Amines ◽  
Metal Free

Transcriptional and post-translational regulation of adiponectin

2009 ◽  
Vol 425 (1) ◽  
pp. 41-52 ◽  
Author(s):  
Meilian Liu ◽  
Feng Liu
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Translational Regulation ◽  
Metabolic Disorders ◽  
Recent Progress ◽  
Serum Levels ◽  
High Molecular Mass ◽  
Adiponectin Gene ◽  
Underlying Mechanisms

Adiponectin is an adipose-tissue-derived hormone with anti-diabetic, anti-atherogenic and anti-inflammatory functions. Adiponectin circulates in the bloodstream in trimeric, hexameric and high-molecular-mass species, and different forms of adiponectin have been found to play distinct roles in the regulation of energy homoeostasis. The serum levels of adiponectin are negatively correlated with obesity and insulin resistance, yet the underlying mechanisms remain elusive. In the present review, we summarize recent progress made on the mechanisms regulating adiponectin gene transcription, multimerization and secretion. We also discuss the potential relevance of these studies to the development of new clinical therapy for insulin resistance, Type 2 diabetes and other obesity-related metabolic disorders.

scholarly journals Re-highlighting the action of PPARγ in treating metabolic diseases

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1127 ◽  
Author(s):  
Sung Hee Choi ◽  
Sung Soo Chung ◽  
Kyong Soo Park
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adverse Effects ◽  
Metabolic Diseases ◽  
Experimental Studies ◽  
Peroxisome Proliferator ◽  
Post Translational Modification ◽  
Atherosclerotic Vascular Disease

Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor family and plays an important role in adipocyte differentiation, glucose homeostasis, and insulin sensitivity. Thiazolidinediones (TZDs), synthetic ligands of PPARγ, have been used for the treatment of diabetes mellitus for two decades. TZDs were expected to be amazing drugs not only for type 2 diabetes but also for metabolic syndrome and atherosclerotic vascular disease because they can reduce both insulin resistance and inflammation in experimental studies. However, serious unwanted effects pushed TZDs back to an optional second-tier drug for type 2 diabetes. Nevertheless, PPARγ is still one of the most important targets for the treatment of insulin resistance and diabetes mellitus, and novel strategies to modulate PPARγ activity to enhance its beneficial effects and reduce unwanted adverse effects are anticipated. Recent studies showed that post-translational modification (PTM) of PPARγ regulates PPARγ activity or stability and may be a novel way to optimize PPARγ activity with reduced adverse effects. In this review, we will focus on recent advances in PTM of PPARγ and the mechanisms regulating PPARγ function as well as in the development of PPARγ modulators or agonists.

scholarly journals Hemorrhagic testicular infarction as a complication of COVID-19 (SARS-CoV-2)

2021 ◽  
Vol 14 (2) ◽  
pp. 70-72
Author(s):  
T.I. Derevyanko ◽  
◽  
S.V. Pridchin ◽  
◽  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Arterial Hypertension ◽  
Blood Clotting ◽  
Clinical Observation ◽  
City Hospital ◽  
Hemorrhagic Infarction ◽  
Testicular Infarction

Introduction. Statistically, adult patients with testicular infarction make up 7-10% of the population of all acute urological pathology. This is one of the urological nosologies, which is а part of a group of diseases called  acute scrotum . Ischemic heart attack occurs as a result of an acute violation of the blood supply to the testicle from the testicular artery. Hemorrhagic infarction usually occurs as a result of impaired microcirculation or embolization of the arteries and arterioles of the testicle and is most often segmental in nature. Conditions associated with increased blood clotting also create conditions for vein obstruction with subsequent tissue necrosis in any organ, including in the testicles. It is known that COVID-19 (SARS-COV-2) causes a pathological increase in blood clotting in the patient's body and it's most dangerous complication is thrombosis in various blood vessels of the patient's organs, which often causes acute ischemia of these organs and even death in patients with COVID 19. Materials and methods. The authors consider 3 similar clinical observations of hemorrhagic testicular infarction in patients suffering from COVID-19 (SARS-COV-2) and who were in the specialized COVID department of the city hospital of Pyatigorsk (Russia, Stavropol Territory). All 3 patients were aged from 67 to 88 years and had a concomitant pathology from the cardiovascular system in the form of arterial hypertension, as well as type 2 diabetes mellitus. The authors provide one case in detail, since all 3 cases followed the same clinical scenario. Clinical observation: Patient B. 66 years old, who was in a specialized COVID department with a diagnosis of: Coronovirus infection caused by COVID 19 (confirmed), moderate form of UO7. 1, community-acquired bilateral lobar pneumonia, acute respiratory distress syndrome, respiratory failure. Concomitant diseases: atherosclerotic cardiosclerosis, arterial hypertension, type 2 diabetes mellitus. The patient received therapy for the underlying disease, but on the 9th day of his stay in the hospital, he had an acute hemorrhagic infarction of the left testicle. The diagnosis was confirmed by laboratory and instrumental examination. An emergency left-sided orchectomy was performed, and the diagnosis was confirmed histologically. Similar clinical situations were observed in two other patients with the same outcome. Conclusions. Hemorrhagic testicular infarction in patients with COVID-19 in our clinical observation can be considered as a complication of COVID-19, or as its clinical manifestation in the organs of the male reproductive system.

scholarly journals Biochemical characterization of the arginine-specific proteases of Porphyromonas gingivalis W50 suggests a common precursor

1997 ◽  
Vol 323 (3) ◽  
pp. 701-709 ◽  
Author(s):  
Minnie RANGARAJAN ◽  
Susan J. M. SMITH ◽  
Sally U ◽  
Michael A. CURTIS
Keyword(s):  
Molecular Mass ◽  
Porphyromonas Gingivalis ◽  
Extracellular Enzymes ◽  
Biochemical Characterization ◽  
Disease Process ◽  
High Molecular Mass ◽  
Kinetic Properties ◽  
Peptidase Activity ◽  
Post Translational Modification ◽  
Peptide Bonds

Extracellular proteases of Porphyromonas gingivalis specific for arginyl peptide bonds are considered to be important virulence factors in periodontal disease. In order to determine the number, inter-relationship and kinetic properties of these proteases, extracellular enzymes with this peptide-bond specificity were purified and characterized from P. gingivalis W50. Three forms, which we denote RI, RI-A and RI-B, accounted for all of the activity in the supernatant. All three enzymes contain an α chain of ∼54 kDa with the same N-terminal amino acid sequence. RI is a heterodimer of non-covalently linked α and β chains which migrate to the same position on SDS/PAGE but which can be resolved by 8 M urea/PAGE. RI-A and RI-B are both monomeric, but the molecular mass of RI-B (70–80 kDa) is significantly increased due to post-translational modification with lipopolysaccharide. All forms show absolute specificity for peptide bonds with Arg in the P1 position and are also capable of hydrolysing N-terminal Arg and C-terminal Arg–Arg peptide bonds. Thus they show limited amino- and carboxy-peptidase activity. For the hydrolysis of Nα-benzoyl-l-Arg-p-nitroanilide, the pH optimum is 8.0 at 30 °C. The Vmax for all three enzymes is controlled by ionization of two residues with apparent pKas at 30 °C of 6.5±0.05 and 9.7±0.05, and ΔH values of ∼29 kJ/mol and ∼ 24 kJ/mol in the enzyme–substrate complex. By analogy with papain, the pKa of 6.5 could be ascribed to a Cys and the pKa of 9.7 to a His residue. E-64 [l-trans-epoxysuccinyl-leucylamide-4-(4-guanidino)butane] is a competitive inhibitor of RI, RI-A and RI-B. Based on physical properties and kinetic behaviour, RI-A appears to be analogous to gingipain from P. gingivalis HG66. However the α/β structure of RI differs significantly from that of the high-molecular-mass multimeric complex of gingipain containing four haemagglutinins described by others. Since the genes for RI and high-molecular-mass gingipain are identical, the data indicate that an alternative processing pathway is involved in the formation of RI from the initial precursor. Furthermore, the identical N-termini and enzymic properties of the catalytic component of RI, RI-A and RI-B suggest that the maturation pathway of the RI precursor may also give rise to RI-A and RI-B. The physiological functions of these isoforms and their role in the disease process may become more apparent through examination of their interactions with host proteins.

scholarly journals Microglial expression of peptidylarginine deiminase 2 in the prenatal rat brain

2007 ◽  
Vol 12 (4) ◽  
Author(s):  
Hiroaki Asaga ◽  
Akihito Ishigami
Keyword(s):  
Polymerase Chain Reaction ◽  
Peptidylarginine Deiminase ◽  
Post Translational Modification ◽  
Chain Reaction ◽  
Morphological Criteria ◽  
Activated State ◽  
The Central Nervous System ◽  
Polymerase Chain ◽  
Arginyl Residues

AbstractPeptidylarginine deiminases (PADs) are Ca2t+-dependant post-translational modification enzymes that catalyze the citrullination of protein arginyl residues. PAD type 2 (PAD2) is thought to be involved in some processes of neurodegeneration and myelination in the central nervous system. In this study, we found PAD2-positive cells in rat cerebra in 19-to 21-day old embryos, i.e. at a developmental stage well before myelination begins. Most of the cells were microglial marker-positive cells found mainly in the prospective medulla, and others were microglial marker-negative cells found mainly in the prospective dentate gyrus of the hippocampus. The former seemed to be in an activated state as judged by morphological criteria. The specificity of the enzyme activity, immunoblotting and reverse transcriptase-polymerase chain reaction analyses revealed that these cells expressed PAD2 and not PAD1, PAD3 or PAD4. Our data is indicative of microglial expression of PAD2 in the prenatal developing cerebrum.

scholarly journals Albumin-mediated alteration of plasma zinc speciation by fatty acids modulates blood clotting in type-2 diabetes

2021 ◽  
Author(s):  
Amélie I. S. Sobczak ◽  
Kondwani G. H. Katundu ◽  
Fladia A. Phoenix ◽  
Siavash Khazaipoul ◽  
Ruitao Yu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Blood Clotting ◽  
Plasma Zinc ◽  
Zinc Speciation

Zn2+ is an essential regulator of coagulation. In plasma, Zn2+ availability is fine-tuned by human serum albumin (HSA). Here we show that elevated fatty acid levels contribute to altered coagulation in type-2 diabetes through Zn2+ mishandling by HSA.

scholarly journals Natural glues and fouling management by interfering with glue curing

2015 ◽  
Vol 20 ◽  
pp. 34
Author(s):  
Daniel Rittschof ◽  
Tara Essock-Burns ◽  
Gary Dickinson ◽  
S. Zmina ◽  
N. Alberman
Keyword(s):  
Blood Clotting ◽  
Larval Settlement ◽  
Modern Technology ◽  
Structural Proteins ◽  
Modern Theory ◽  
Biological Processes ◽  
Small Peptides ◽  
Binding Domains ◽  
Enzymatic Activation ◽  
Biological Glues

Multidisciplinary approaches and modern technology provide insights to glue curing that are stimulatingand controversial. Our team applies classic and modern theory and techniques to the study of barnacle glue. Techniques include physical measures, bacteriology, behavior, physiology, biochemistry, microscopy, spectroscopy, tomography, tandem mass spectrometry, molecular biology and proteomics. Theory is grounded in evolution and previous literature. Here, we use data from these techniques to support the hypothesis that barnacle glue curing is similar toblood clotting and propose a model for how glue cures. Similar to blood clotting, barnacle glue curing involves enzymatic activation of precursors and rearrangement of structural molecules to form a crosslinked material. Barnacle larval settlement, bacteriology and biochemical data show glue contains large amounts of small peptides. Their role in glue curing has been overlooked. The peptides comprise 15 to 30% of partially cured glue. Because they have little secondary structure, the peptides can associate with binding domains on the substrate and interface with the larger, well-described structural proteins known in barnacle glue. Enzymes participate in curing of barnacle glue. Siloxanes impact glue-curing enzymes. They potentiate trypsin activity and inhibit transglutaminase activity. Changing enzymeactivity impacts how glue cures. Disrupting the curing process of biological glues is central to effective cleaning strategies for fouling management. Thus silicones that interfere with enzyme activity have potential as additives in easy cleansurfaces. The environmental impacts of organosilicones that are generated by biological processes need to be addressed 

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