DIABETES-POST-TRANSLATIONAL PROTEIN MODIFICATION FOR DEVELOPMENT OF NEW DRUGS

INDIAN DRUGS ◽  
2014 ◽  
Vol 51 (09) ◽  
pp. 5-11
Author(s):  
P Menon ◽  
◽  
M S Kumar
Keyword(s):  
Glucose Level ◽  
Protein Modification ◽  
Epigenetic Modification ◽  
The Body ◽  
New Drugs ◽  
Metabolic Memory ◽  
Peroxisome Proliferator ◽  
Post Translational Modification ◽  
High Molecular Weight Adiponectin ◽  
Post Translational Modifications

Diabetes is a disorder associated with improper use of glucose by the body leading to increased level of glucose in the blood stream. Beta cells in the pancreas produce the hormone insulin, which is responsible for the movement of glucose into cells where it is utilized to produce energy. Due to the shortage of insulin in diabetic condition, the level of glucose in the bloodstream increases. The level of glucose within cells fall and thus the cells are not able to produce energy using glucose. It also gives rise to various other complications such as blindness, kidney failure, numbness in toes, delayed wound healing, cardiovascular complications, weight gain, loss of consciousness, disorientation etc. which in itself may be dangerous. The root cause of diabetes may either be lack of insulin being produced by the pancreas or development of resistance towards insulin leading to no effect of insulin on the glucose level. Post-translational modifications of protein control various biological processes. It is also considered as an important process in the pathogenesis of diabetes mellitus.In the current review, we will discuss the recent developments in post translational modification of genes associated with diabetes as well as epigenetic modification and metabolic memory that maybe responsible for the onset of diabetes and its associated complications. Currently research is being conducted on high molecular weight adiponectin, peroxisome proliferator-activated receptors (PPARγ), epigenetic histone modifications and Calpain 10 (CAPN10 gene encoded) protein based upon the post translational modifications they undergo and how these modifications affect glucose level regulation. This review article aims at shedding light upon recent advances in biotechnology that are focussed on studying the nature of protein modifications that result in diabetes and finding ways to prevent these modifications or stimulate a new modification that may result in better control of the disease state if not a cure.

scholarly journals Profiling of lysine-acetylated proteins in human urine

2017 ◽  
Author(s):  
Weiwei Qin ◽  
Zhenhuan Du ◽  
He Huang ◽  
Youhe Gao
Keyword(s):  
Human Urine ◽  
High Resolution Mass Spectrometry ◽  
The Body ◽  
Lysine Acetylation ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Normal Human ◽  
Measurable Change

AbstractBiomarker is the measurable change associated with a physiological or pathophysiological process, its nature is change. Contrast to the blood which is under homeostatic controls, urine reflects changes in the body earlier and more sensitive therefore is a better biomarker source. Lysine acetylation is an abundant and highly regulated post-translational modification. It plays a pivotal role in modulating diverse biological processes and is associated with various important diseases. Enrichment or visualization of proteins with specific post-translational modifications provides a method for sampling the urinary proteome and reducing sample complexity. In this study, we used anti-acetyllysine antibody-based immunoaffinity enrichment combined with high-resolution mass spectrometry to profile lysine-acetylated proteins in normal human urine. A total of 629 acetylation sites on 315 proteins were identified, including some very low-abundance proteins. This is the first proteome-wide characterization of lysine acetylation proteins in normal human urine. Our dataset provides a useful resource for the further discovery of the lysine acetylated proteins as biomarker in urine.

scholarly journals Bioinformatics analysis and collection of protein post-translational modification sites in human viruses

2020 ◽  
Author(s):  
Yujia Xiang ◽  
Quan Zou ◽  
Lilin Zhao
Keyword(s):  
Viral Protein ◽  
Protein Modification ◽  
Phosphorylation Site ◽  
Protein Domains ◽  
Human Interaction ◽  
Phosphorylation Sites ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Human Proteins ◽  
Human Viruses

AbstractIn viruses, post-translational modifications (PTMs) are essential for their life cycle. Recognizing viral PTMs is very important for better understanding the mechanism of viral infections and finding potential drug targets. However, few studies have investigated the roles of viral PTMs in virus-human interactions using comprehensive viral PTM datasets. To fill this gap, firstly, we developed a viral post-translational modification database (VPTMdb) for collecting systematic information of viral PTM data. The VPTMdb contains 912 PTM sites that integrate 414 experimental-confirmed PTM sites with 98 proteins in 45 human viruses manually extracted from 162 publications and 498 PTMs extracted from UniProtKB/Swiss-Prot. Secondly, we investigated the viral PTM sequence motifs, the function of target human proteins, and characteristics of PTM protein domains. The results showed that (i) viral PTMs have the consensus motifs with human proteins in phosphorylation, SUMOylation and N-glycosylation. (ii) The function of human proteins that targeted by viral PTM proteins are related to protein targeting, translation, and localization. (iii) Viral PTMs are more likely to be enriched in protein domains. The findings should make an important contribution to the field of virus-human interaction. Moreover, we created a novel sequence-based classifier named VPTMpre to help users predict viral protein phosphorylation sites. Finally, an online web server was implemented for users to download viral protein PTM data and predict phosphorylation sites of interest.Author summaryPost-translational modifications (PTMs) plays an important role in the regulation of viral proteins; However, due to the limitation of data sets, there has been no detailed investigation of viral protein PTMs characteristics. In this manuscript, we collected experimentally verified viral protein post-translational modification sites and analysed viral PTMs data from a bioinformatics perspective. Besides, we constructed a novel feature-based machine learning model for predicting phosphorylation site. This is the first study to explore the roles of viral protein modification in virus infection using computational methods. The valuable viral protein PTM data resource will provide new insights into virus-host interaction.

scholarly journals The interaction of canonical Wnt/β-catenin signaling with protein lysine acetylation

2022 ◽  
Vol 27 (1) ◽  
Author(s):  
Hongjuan You ◽  
Qi Li ◽  
Delong Kong ◽  
Xiangye Liu ◽  
Fanyun Kong ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Protein Function ◽  
Protein Modification ◽  
Epigenetic Modification ◽  
Lysine Acetylation ◽  
Protein Acetylation ◽  
Post Translational Modification ◽  
Histone Protein ◽  
Protein Lysine Acetylation ◽  
Canonical Wnt

AbstractCanonical Wnt/β-catenin signaling is a complex cell-communication mechanism that has a central role in the progression of various cancers. The cellular factors that participate in the regulation of this signaling are still not fully elucidated. Lysine acetylation is a significant protein modification which facilitates reversible regulation of the target protein function dependent on the activity of lysine acetyltransferases (KATs) and the catalytic function of lysine deacetylases (KDACs). Protein lysine acetylation has been classified into histone acetylation and non-histone protein acetylation. Histone acetylation is a kind of epigenetic modification, and it can modulate the transcription of important biological molecules in Wnt/β-catenin signaling. Additionally, as a type of post-translational modification, non-histone acetylation directly alters the function of the core molecules in Wnt/β-catenin signaling. Conversely, this signaling can regulate the expression and function of target molecules based on histone or non-histone protein acetylation. To date, various inhibitors targeting KATs and KDACs have been discovered, and some of these inhibitors exert their anti-tumor activity via blocking Wnt/β-catenin signaling. Here, we discuss the available evidence in understanding the complicated interaction of protein lysine acetylation with Wnt/β-catenin signaling, and lysine acetylation as a new target for cancer therapy via controlling this signaling.

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.

Unrestrictive protein modification localization and quality control for open search of mass spectra

2018 ◽  
Author(s):  
Zhiwu An ◽  
Fuzhou Gong ◽  
Yan Fu
Keyword(s):  
Mass Spectrometry ◽  
Quality Control ◽  
Tandem Mass Spectrometry ◽  
Mass Spectra ◽  
Protein Modification ◽  
Software Tool ◽  
Tandem Mass ◽  
Simulation Data ◽  
Post Translational Modifications

We have developed PTMiner, a first software tool for automated, confident filtering, localization and annotation of protein post-translational modifications identified by open (mass-tolerant) search of large tandem mass spectrometry datasets. The performance of the software was validated on carefully designed simulation data. <br>

The Involvement of Post-Translational Modifications in Alzheimer's Disease

2018 ◽  
Vol 15 (4) ◽  
pp. 313-335 ◽  
Author(s):  
Serena Marcelli ◽  
Massimo Corbo ◽  
Filomena Iannuzzi ◽  
Lucia Negri ◽  
Fabio Blandini ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Modification ◽  
Neurodegenerative Disorder ◽  
Amyloid Β ◽  
Normal Function ◽  
Ageing Population ◽  
Covalent Bonds ◽  
Post Translational Modifications ◽  
Related Proteins

Background: Alzheimer's disease (AD) is a neurodegenerative disorder recognized as the most common cause of chronic dementia among the ageing population. AD is histopathologically characterized by progressive loss of neurons and deposits of insoluble proteins, primarily composed of amyloid-β pelaques and neurofibrillary tangles (NFTs). Methods: Several molecular processes contribute to the formation of AD cellular hallmarks. Among them, post-translational modifications (PTMs) represent an attractive mechanism underlying the formation of covalent bonds between chemical groups/peptides to target proteins, which ultimately result modified in their function. Most of the proteins related to AD undergo PTMs. Several recent studies show that AD-related proteins like APP, Aβ, tau, BACE1 undergo post-translational modifications. The effect of PTMs contributes to the normal function of cells, although aberrant protein modification, which may depend on many factors, can drive the onset or support the development of AD. Results: Here we will discuss the effect of several PTMs on the functionality of AD-related proteins potentially contributing to the development of AD pathology. Conclusion: We will consider the role of Ubiquitination, Phosphorylation, SUMOylation, Acetylation and Nitrosylation on specific AD-related proteins and, more interestingly, the possible interactions that may occur between such different PTMs.

A multi-method and structure-based in silico vaccine designing against Helicobacter pylori employing immuno-informatics approach

2020 ◽  
Vol 17 ◽  
Author(s):  
Anam Naz ◽  
Tahreem Zaheer ◽  
Hamza Arshad Dar ◽  
Faryal Mehwish Awan ◽  
Ayesha Obaid ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Vaccine Development ◽  
Amino Acid Sequences ◽  
The Body ◽  
New Drugs ◽  
Toll Like Receptor ◽  
Peptide Vaccines ◽  
Hla Alleles ◽  
Vaccine Candidates ◽  
H Pylori

Background: Helicobacter pylori infection and its treatment still remains a challenge to human health worldwide. A variety of antibiotics and combination therapies are currently used to treat H. pylori induced ulcers and carcinoma; however, no effective treatment is available to eliminate the pathogen from the body. Additionally, antibiotic resistance is also one of the main reasons for prolonged and persistent infection. Aim of the study: Until new drugs are available for this infection, vaccinology seems the only alternative opportunity to exploit against H. pylori induced diseases. Methods: Multiple epitopes prioritized in our previous study have been tested for their possible antigenic combinations, and results in 169-mer and 183-mer peptide vaccines containing the amino acid sequences of 3 and 4 epitopes respectively, along with adjuvant (Cholera Toxin Subunit B adjuvant at 5’ end) and linkers (GPGPG and EAAAK). Results: Poly-epitope proteins proposed as potential vaccine candidates against H. pylori include SabAHP0289-Omp16-VacA (SHOV), VacA-Omp16-HP0289-FecA (VOHF), VacA-Omp16-HP0289-SabA (VOHS), VacA-Omp16-HP0289-BabA (VOHB), VacA-Omp16-HP0289-SabA-FecA (VOHSF), VacAOmp16-HP0289-SabA-BabA (VOHSB) and VacA-Omp16-HP0289-BabA-SabA (VOHBS). Structures of these poly-epitope peptide vaccines have been modelled and checked for their affinity with HLA alleles and receptors. These proposed poly-epitope vaccine candidates bind efficiently with A2, A3, B7 and DR1 superfamilies of HLA alleles. They can also form stable and significant interactions with Toll-like receptor 2 and Toll-like receptor 4. Conclusion: Results suggest that these multi-epitopic vaccines can elicit a significant immune response against H. pylori and can be tested further for efficient vaccine development.

scholarly journals Immunological discrimination of β-tubulin isoforms in developing mouse brain. Post-translational modification of non-class-III β-tubulins

1992 ◽  
Vol 288 (3) ◽  
pp. 919-924 ◽  
Author(s):  
I Linhartová ◽  
P Dráber ◽  
E Dráberová ◽  
V Viklický
Keyword(s):  
Mouse Brain ◽  
Specific Class ◽  
Class Iii ◽  
Post Translational Modification ◽  
Beta Tubulin ◽  
Developmentally Regulated ◽  
Post Translational Modifications ◽  
Tubulin Isotypes ◽  
Tubulin Isoforms ◽  
Developing Mouse Brain

Individual beta-tubulin isoforms in developing mouse brain were characterized using immunoblotting, after preceding high-resolution isoelectric focusing, with monoclonal antibodies against different structural regions of beta-tubulin. Some of the antibodies reacted with a limited number of tubulin isoforms in all stages of brain development and in HeLa cells. The epitope for the TU-14 antibody was located in the isotype-defining domain and was present on the beta-tubulin isotypes of classes I, II and IV, but absent on the neuron-specific class-III isotype. The data suggest that non-class-III beta-tubulins in mouse brain are substrates for developmentally regulated post-translational modifications and that beta-tubulins of non-neuronal cells are also post-translationally modified.

scholarly journals Hypoglycemic and antioxidative activities of ethanol seed extract of Hunteria umbellate (Hallier F.) on streptozotocin-induced diabetic rats

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Olubanke O. Ogunlana ◽  
Babatunde O. Adetuyi ◽  
Miracle Rotimi ◽  
lohor Esalomi ◽  
Alaba Adeyemi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Glucose ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Seed Extract ◽  
The Body ◽  
High Concentration ◽  
Group 5

Abstract Background Diabetes, a global cause of mortality in developing countries is a chronic disorder affecting the metabolism of macromolecules and has been attributed to the defective production and action of insulin characterized by persistent hyperglycemic properties. This global disorder harms organs of the body such as the liver, kidney and spleen. Medicinal plants such as Hunteria umbellate have been shown to possess hypoglycemic, antioxidative and anti-diabetic properties owing to the high concentration of active phytochemical constituents like flavonoids and alkaloids. The present study seeks to evaluate the hypoglycemic activities of ethanolic seed extract of Hunteria umbellate on streptozotocin-induced diabetes rats. Methods Thirty (30) female experimental rats were randomly divided into five groups with six rats per group and were administered streptozotocin (STZ) and Hunteria umbellate as follows. Group 1 served as control and was given only distilled water, group 2 rats were administered 60 mg/kg STZ; Group 3 was administered 60 mg/kg STZ and 100 mg/kg metformin; group 4 rats were administered 60 mg/kg STZ and 800 mg/kg Hunteria umbellate, group 5 rats 60 mg/kg STZ and 400 mg/kg Hunteria umbellate. The fasting blood glucose level of each rat was measured before sacrifice. Rats were then sacrificed 24 h after the last dose of treatment. Results The results showed that Hunteria umbellate significantly reversed STZ-induced increase in fasting blood glucose and increase in body and organs weight of rats. Hunteria umbellate significantly reversed STZ-induced decrease in antioxidant enzyme in liver, kidney and spleen of rats. Hunteria umbellate significantly reversed STZ-induced increase in oxidative stress markers in liver, kidney and spleen of rats. Conclusion Collectively, our results provide convincing information that inhibition of oxidative stress and regulation of blood glucose level are major mechanisms through which Hunteria umbellate protects against streptozotocin-induced diabketes rats.

Sign in / Sign up

Export Citation Format

Share Document