Protein CoAlation: a redox-linked post-translational modification

2017 ◽  
Vol 474 (16) ◽  
pp. 2897-2899 ◽  
Author(s):  
Steven C. Ley ◽  
Luiz Pedro S. de Carvalho
Keyword(s):  
Mass Spectrometry ◽  
Signal Transduction ◽  
Metabolic Pathways ◽  
Metabolic Response ◽  
Metabolic Stress ◽  
Regulatory Activity ◽  
Post Translational Modification ◽  
Target Proteins ◽  
Biochemical Journal ◽  
Response To Stress

Regulation of metabolic pathways by signal transduction and transcriptional cascades can alter cellular levels of metabolites. Metabolites themselves can also have regulatory activity as shown in a new study published in the Biochemical Journal. Tsuchiya et al. describe a novel antibody and mass spectrometry-based method for identifying proteins that are reversibly modified with Coenzyme A (CoA). Analysis of the ‘CoAlated proteome’ under conditions of oxidative and metabolic stress revealed a bias towards the modification of metabolic enzymes by CoA. Furthermore, CoAlation was shown to alter the activity of target proteins. These results suggest that CoAlation is a widespread post-translational modification that may have important roles in the metabolic response to stress.

Glycome profiling using modern glycomics technology: technical aspects and applications

2010 ◽  
Vol 391 (2/3) ◽  
Author(s):  
Dieter Vanderschaeghe ◽  
Nele Festjens ◽  
Joris Delanghe ◽  
Nico Callewaert
Keyword(s):  
Mass Spectrometry ◽  
Signal Transduction ◽  
Liquid Chromatography Mass Spectrometry ◽  
Post Translational Modification ◽  
Technical Aspects ◽  
Glycome Profiling ◽  
The Past ◽  
Research Fields ◽  
Research Goal ◽  
Glycan Profiling

Abstract Glycomics research has become indispensable in many research fields such as immunity, signal transduction and development. Moreover, changes in the glycosylation of proteins and lipids have been reported in several diseases including cancer. The analysis of a complex post-translational modification such as glycosylation depends on the availability or development of appropriate analytical technologies. The research goal determines the sensitivity, resolution and throughput requirements and guides the choice of a particular technology. This review highlights the evolution of glycan profiling tools in the past 5 years. We focus on capillary electrophoresis, liquid chromatography, mass spectrometry and lectin microarrays.

Dicarbonyl derived post-translational modifications: chemistry bridging biology and aging-related disease

2020 ◽  
Vol 64 (1) ◽  
pp. 97-110
Author(s):  
Christian Sibbersen ◽  
Mogens Johannsen
Keyword(s):  
Mass Spectrometry ◽  
Future Research ◽  
Amino Acid Residues ◽  
Post Translational Modification ◽  
Dicarbonyl Compounds ◽  
Protein Targets ◽  
Post Translational Modifications ◽  
Reactive Protein ◽  
Glycation End Products ◽  
Direct Mass Spectrometry

Abstract In living systems, nucleophilic amino acid residues are prone to non-enzymatic post-translational modification by electrophiles. α-Dicarbonyl compounds are a special type of electrophiles that can react irreversibly with lysine, arginine, and cysteine residues via complex mechanisms to form post-translational modifications known as advanced glycation end-products (AGEs). Glyoxal, methylglyoxal, and 3-deoxyglucosone are the major endogenous dicarbonyls, with methylglyoxal being the most well-studied. There are several routes that lead to the formation of dicarbonyl compounds, most originating from glucose and glucose metabolism, such as the non-enzymatic decomposition of glycolytic intermediates and fructosyl amines. Although dicarbonyls are removed continuously mainly via the glyoxalase system, several conditions lead to an increase in dicarbonyl concentration and thereby AGE formation. AGEs have been implicated in diabetes and aging-related diseases, and for this reason the elucidation of their structure as well as protein targets is of great interest. Though the dicarbonyls and reactive protein side chains are of relatively simple nature, the structures of the adducts as well as their mechanism of formation are not that trivial. Furthermore, detection of sites of modification can be demanding and current best practices rely on either direct mass spectrometry or various methods of enrichment based on antibodies or click chemistry followed by mass spectrometry. Future research into the structure of these adducts and protein targets of dicarbonyl compounds may improve the understanding of how the mechanisms of diabetes and aging-related physiological damage occur.

Review of Progress in Predicting Protein Methylation Sites

2019 ◽  
Vol 23 (15) ◽  
pp. 1663-1670 ◽  
Author(s):  
Chunyan Ao ◽  
Shunshan Jin ◽  
Yuan Lin ◽  
Quan Zou
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Transcriptional Activity ◽  
Regulation Of Gene Expression ◽  
Protein Methylation ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Regulatory Enzymes ◽  
Lysine Residues ◽  
Arginine Residues

Protein methylation is an important and reversible post-translational modification that regulates many biological processes in cells. It occurs mainly on lysine and arginine residues and involves many important biological processes, including transcriptional activity, signal transduction, and the regulation of gene expression. Protein methylation and its regulatory enzymes are related to a variety of human diseases, so improved identification of methylation sites is useful for designing drugs for a variety of related diseases. In this review, we systematically summarize and analyze the tools used for the prediction of protein methylation sites on arginine and lysine residues over the last decade.

scholarly journals N-Terminomics Strategies for Protease Substrates Profiling

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4699
Author(s):  
Mubashir Mintoo ◽  
Amritangshu Chakravarty ◽  
Ronak Tilvawala
Keyword(s):  
Mass Spectrometry ◽  
Protease Activity ◽  
Viral Infections ◽  
Mass Spectrometry Analysis ◽  
Post Translational Modification ◽  
Spectrometry Analysis ◽  
Physiological Conditions ◽  
Inflammatory Conditions ◽  
Biological Mixtures

Proteases play a central role in various biochemical pathways catalyzing and regulating key biological events. Proteases catalyze an irreversible post-translational modification called proteolysis by hydrolyzing peptide bonds in proteins. Given the destructive potential of proteolysis, protease activity is tightly regulated. Dysregulation of protease activity has been reported in numerous disease conditions, including cancers, neurodegenerative diseases, inflammatory conditions, cardiovascular diseases, and viral infections. The proteolytic profile of a cell, tissue, or organ is governed by protease activation, activity, and substrate specificity. Thus, identifying protease substrates and proteolytic events under physiological conditions can provide crucial information about how the change in protease regulation can alter the cellular proteolytic landscape. In recent years, mass spectrometry-based techniques called N-terminomics have become instrumental in identifying protease substrates from complex biological mixtures. N-terminomics employs the labeling and enrichment of native and neo-N-termini peptides, generated upon proteolysis followed by mass spectrometry analysis allowing protease substrate profiling directly from biological samples. In this review, we provide a brief overview of N-terminomics techniques, focusing on their strengths, weaknesses, limitations, and providing specific examples where they were successfully employed to identify protease substrates in vivo and under physiological conditions. In addition, we explore the current trends in the protease field and the potential for future developments.

scholarly journals The Multifaceted Roles of USP15 in Signal Transduction

2021 ◽  
Vol 22 (9) ◽  
pp. 4728
Author(s):  
Tanuza Das ◽  
Eun Joo Song ◽  
Eunice EunKyeong Kim
Keyword(s):  
Signal Transduction ◽  
Signaling Pathways ◽  
Cellular Networks ◽  
Clinical Applications ◽  
Regulatory Mechanisms ◽  
Signaling Networks ◽  
Post Translational Modification ◽  
Comprehensive Overview ◽  
E3 Ligases ◽  
Disease Markers

Ubiquitination and deubiquitination are protein post-translational modification processes that have been recognized as crucial mediators of many complex cellular networks, including maintaining ubiquitin homeostasis, controlling protein stability, and regulating several signaling pathways. Therefore, some of the enzymes involved in ubiquitination and deubiquitination, particularly E3 ligases and deubiquitinases, have attracted attention for drug discovery. Here, we review recent findings on USP15, one of the deubiquitinases, which regulates diverse signaling pathways by deubiquitinating vital target proteins. Even though several basic previous studies have uncovered the versatile roles of USP15 in different signaling networks, those have not yet been systematically and specifically reviewed, which can provide important information about possible disease markers and clinical applications. This review will provide a comprehensive overview of our current understanding of the regulatory mechanisms of USP15 on different signaling pathways for which dynamic reverse ubiquitination is a key regulator.

scholarly journals Transcriptional Response in the Digestive Gland of the King Scallop (Pecten maximus) after the Injection of Domoic Acid

Toxins ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 339
Author(s):  
Pablo Ventoso ◽  
Antonio J. Pazos ◽  
Juan Blanco ◽  
M. Luz Pérez-Parallé ◽  
Juan C. Triviño ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Gene Ontology ◽  
Immune System ◽  
Digestive Gland ◽  
Domoic Acid ◽  
Differentially Expressed ◽  
Pecten Maximus ◽  
System Process ◽  
Immune System Process ◽  
Response To Stress

Some diatom species of the genus Pseudo-nitzschia produce the toxin domoic acid. The depuration rate of domoic acid in Pecten maximus is very low; for this reason, king scallops generally contain high levels of domoic acid in their tissues. A transcriptomic approach was used to identify the genes differentially expressed in the P. maximus digestive gland after the injection of domoic acid. The differential expression analysis found 535 differentially expressed genes (226 up-regulated and 309 down-regulated). Protein–protein interaction networks obtained with the up-regulated genes were enriched in gene ontology terms, such as vesicle-mediated transport, response to stress, signal transduction, immune system process, RNA metabolic process, and autophagy, while networks obtained with the down-regulated genes were enriched in gene ontology terms, such as response to stress, immune system process, ribosome biogenesis, signal transduction, and mRNA processing. Genes that code for cytochrome P450 enzymes, glutathione S-transferase theta-1, glutamine synthase, pyrroline-5-carboxylate reductase 2, and sodium- and chloride-dependent glycine transporter 1 were among the up-regulated genes. Therefore, a stress response at the level of gene expression, that could be caused by the domoic acid injection, was evidenced by the alteration of several biological, cellular, and molecular processes.

scholarly journals Placental 13C-DHA metabolism and relationship with maternal BMI, glycemia and birthweight

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Oliver C. Watkins ◽  
Preben Selvam ◽  
Reshma Appukuttan Pillai ◽  
Victoria K. B. Cracknell-Hazra ◽  
Hannah E. J. Yong ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Lipid Metabolism ◽  
Metabolic Pathways ◽  
Liquid Chromatography Mass Spectrometry ◽  
Fasting Glycemia ◽  
Glucose Treatment ◽  
Maternal Bmi

Abstract Background Fetal docosahexaenoic acid (DHA) supply relies on preferential transplacental transfer, which is regulated by placental DHA lipid metabolism. Maternal hyperglycemia and obesity associate with higher birthweight and fetal DHA insufficiency but the role of placental DHA metabolism is unclear. Methods Explants from 17 term placenta were incubated with 13C-labeled DHA for 48 h, at 5 or 10 mmol/L glucose treatment, and the production of 17 individual newly synthesized 13C-DHA labeled lipids quantified by liquid chromatography mass spectrometry. Results Maternal BMI positively associated with 13C-DHA-labeled diacylglycerols, triacylglycerols, lysophospholipids, phosphatidylcholine and phosphatidylethanolamine plasmalogens, while maternal fasting glycemia positively associated with five 13C-DHA triacylglycerols. In turn, 13C-DHA-labeled phospholipids and triacylglycerols positively associated with birthweight centile. In-vitro glucose treatment increased most 13C-DHA-lipids, but decreased 13C-DHA phosphatidylethanolamine plasmalogens. However, with increasing maternal BMI, the magnitude of the glucose treatment induced increase in 13C-DHA phosphatidylcholine and 13C-DHA lysophospholipids was curtailed, with further decline in 13C-DHA phosphatidylethanolamine plasmalogens. Conversely, with increasing birthweight centile glucose treatment induced increases in 13C-DHA triacylglycerols were exaggerated, while glucose treatment induced decreases in 13C-DHA phosphatidylethanolamine plasmalogens were diminished. Conclusions Maternal BMI and glycemia increased the production of different placental DHA lipids implying impact on different metabolic pathways. Glucose-induced elevation in placental DHA metabolism is moderated with higher maternal BMI. In turn, findings of associations between many DHA lipids with birthweight suggest that BMI and glycemia promote fetal growth partly through changes in placental DHA metabolism.

scholarly journals Protein Turnover Measurements in Human Serum by Serial Immunoaffinity LC-MS/MS

2018 ◽  
Vol 64 (2) ◽  
pp. 279-288 ◽  
Author(s):  
Vahid Farrokhi ◽  
Xiaoying Chen ◽  
Hendrik Neubert
Keyword(s):  
Mass Spectrometry ◽  
Cell Adhesion ◽  
Human Serum ◽  
Adhesion Molecule ◽  
Protein Turnover ◽  
Cell Adhesion Molecule ◽  
Analytical Sensitivity ◽  
Target Proteins ◽  
Cell Adhesion Molecule 1 ◽  
Sample Set

Abstract BACKGROUND The half-life of target proteins is frequently an important parameter in mechanistic pharmacokinetic and pharmacodynamic (PK/PD) modeling of biotherapeutics. Clinical studies for accurate measurement of physiologically relevant protein turnover can reduce the uncertainty in PK/PD model-based predictions, for example, of the therapeutic dose and dosing regimen in first-in-human clinical trials. METHODS We used a targeted mass spectrometry work flow based on serial immunoaffinity enrichment ofmultiple human serum proteins from a [5,5,5-2H3]-L-leucine tracer pulse-chase study in healthy volunteers. To confirm the reproducibility of turnover measurements from serial immunoaffinity enrichment, multiple aliquots from the same sample set were subjected to protein turnover analysis in varying order. Tracer incorporation was measured by multiple–reaction-monitoring mass spectrometry and target turnover was calculated using a four-compartment pharmacokinetic model. RESULTS Five proteins of clinical or therapeutic relevance including soluble tumor necrosis factor receptor superfamily member 12A, tissue factor pathway inhibitor, soluble interleukin 1 receptor like 1, soluble mucosal addressin cell adhesion molecule 1, and muscle-specific creatine kinase were sequentially subjected to turnover analysis from the same human serum sample. Calculated half-lives ranged from 5–15 h; however, no tracer incorporation was observed for mucosal addressin cell adhesion molecule 1. CONCLUSIONS The utility of clinical pulse-chase studies to investigate protein turnover can be extended by serial immunoaffinity enrichment of target proteins. Turnover analysis from serum and subsequently from remaining supernatants provided analytical sensitivity and reproducibility for multiple human target proteins in the same sample set, irrespective of the order of analysis.

A system model of the metabolic response to stress

1983 ◽  
Vol 28 (4) ◽  
pp. 268-273 ◽  
Author(s):  
Carta Atkinson ◽  
John H. Milsum
Keyword(s):  
Metabolic Response ◽  
System Model ◽  
Response To Stress

scholarly journals Metabolomics in nutrition research–a powerful window into nutritional metabolism

2016 ◽  
Vol 60 (5) ◽  
pp. 451-458 ◽  
Author(s):  
Lorraine Brennan
Keyword(s):  
Mass Spectrometry ◽  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Data Acquisition ◽  
Small Molecules ◽  
Biological Samples ◽  
Metabolic Pathways ◽  
Recent Trend ◽  
Disease States ◽  
Nutrition Research

Metabolomics is the study of small molecules present in biological samples. In recent years it has become evident that such small molecules, called metabolites, play a key role in the development of disease states. Furthermore, metabolomic applications can reveal information about alterations in certain metabolic pathways under different conditions. Data acquisition in metabolomics is usually performed using nuclear magnetic resonance (NMR)-based approaches or mass spectrometry (MS)-based approaches with a more recent trend including the application of multiple platforms in order to maximise the coverage in terms of metabolites measured. The application of metabolomics is rapidly increasing and the present review will highlight applications in nutrition research.

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