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https://www.readbyqxmd.com/read/29322920/investigation-and-identification-of-functional-post-translational-modification-sites-associated-with-drug-binding-and-protein-protein-interactions
#1
Min-Gang Su, Julia Tzu-Ya Weng, Justin Bo-Kai Hsu, Kai-Yao Huang, Yu-Hsiang Chi, Tzong-Yi Lee
BACKGROUND: Protein post-translational modification (PTM) plays an essential role in various cellular processes that modulates the physical and chemical properties, folding, conformation, stability and activity of proteins, thereby modifying the functions of proteins. The improved throughput of mass spectrometry (MS) or MS/MS technology has not only brought about a surge in proteome-scale studies, but also contributed to a fruitful list of identified PTMs. However, with the increase in the number of identified PTMs, perhaps the more crucial question is what kind of biological mechanisms these PTMs are involved in...
December 21, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/29311131/posttranslational-modifications-of-ras-proteins
#2
Ian Ahearn, Mo Zhou, Mark R Philips
The three human RAS genes encode four proteins that play central roles in oncogenesis by acting as binary molecular switches that regulate signaling pathways for growth and differentiation. Each is subject to a set of posttranslational modifications (PTMs) that modify their activity or are required for membrane targeting. The enzymes that catalyze the various PTMs are potential targets for anti-RAS drug discovery. The PTMs of RAS proteins are the focus of this review.
January 8, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29301074/genetically-incorporating-two-distinct-post-translational-modifications-into-one-protein-simultaneously
#3
Sumana Venkat, Jourdan Sturges, Alleigh Stahman, Caroline Gregory, Qinglei Gan, Chenguang Fan
Post-translational modifications (PTMs) play important roles in regulating a variety of biological processes. To facilitate PTM studies, the genetic code expansion strategy has been utilized to co-translationally incorporate individual PTMs such as acetylation and phosphorylation into proteins at specific sites. However, recent studies have demonstrated that PTMs actually work together to regulate protein functions and structures. Thus, simultaneous incorporation of multiple distinct PTMs into one protein is highly desirable...
January 4, 2018: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29288197/recruitment-and-allosteric-stimulation-of-a-histone-deubiquitinating-enzyme-during-heterochromatin-assembly
#4
Alexis Zukowksi, Nouf Omar Al-Afaleq, Emily D Duncan, Tingting Yao, Aaron M Johnson
Heterochromatin formation in budding yeast is regulated by the silent information regulator (SIR) complex. The SIR complex comprises the NAD-dependent deacetylase Sir2, the scaffolding protein Sir4, and the nucleosome-binding protein Sir3. Transcriptionally active regions present a challenge to SIR complex-mediated de novo heterochromatic silencing due to the presence of antagonistic histone PTMs, including acetylation and methylation. Methylation of histone H3K4 and H3K79 are dependent on mono-ubiquitination of histone H2B (H2B-Ub)...
December 29, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29283250/sensitive-western-blot-analysis-of-azide-tagged-protein-post-translational-modifications-ptms-using-thermo-responsive-polymer-self-assembly
#5
Tong Liu, Wanjun Zhang, Zheng Zhang, Ming-Li Chen, Jian-Hua Wang, Xiaohong Qian, Weijie Qin
Western-blot (WB) is a powerful analytical technique for protein identification in complex biological samples and has been widely used in biological studies for decades. Detection specificity and sensitivity of WB largely relies on quality of the antibodies and performance of the conjugated HRP. However, the application of WB analysis for the detection of protein post-translational modifications (PTMs) is hampered by the low abundance of protein PTMs and by the limited availability of antibodies that specifically differentiate various kinds of PTMs from their protein substrates...
December 28, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29278491/imtbx-and-grppr-software-for-top-down-proteomics-utilizing-ion-mobility-mass-spectrometry
#6
Dmitry M Avtonomov, Daniel A Polasky, Brandon T Ruotolo, Alexey I Nesvizhskii
Top-down proteomics has emerged as a transformative method for the analysis of protein sequence and post-translational modifications (PTMs). Top-down experiments have historically been performed primarily on ultra-high resolution mass spectrometers due to the complexity of spectra resulting from fragmentation of intact proteins, but recent advances in coupling ion mobility separations to faster, lower resolution mass analyzers now offer a viable alternative. However, software capable of interpreting the highly complex 2-dimensional spectra that result from coupling ion mobility separation to top-down experiments is currently lacking...
December 26, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29276666/reciprocal-regulation-of-ppar%C3%AE-and-runx2-activities-in-marrow-mesenchymal-stem-cells-fine-balance-between-p38-mapk-and-protein-phosphatase-5
#7
Lance A Stechschulte, Beata Lecka-Czernik
Purpose of review: Post-translational modifications (PTMs), specifically serine phosphorylation, are essential for determination and tuning up an activity of many proteins, including those that are involved in the control of gene transcription. Transcription factors PPARγ2 and RUNX2 are essential for mesenchymal stem cell (MSC) commitment to either adipocyte or osteoblast lineage. This review is summarizing current knowledge how serine phosphorylation PTMs regulate activities of both transcription factors and MSCs lineage commitment...
June 2017: Current Molecular Biology Reports
https://www.readbyqxmd.com/read/29262339/regulation-of-h3k4me3-at-transcriptional-enhancers-characterizes-acquisition-of-virus-specific-cd8-t-cell-lineage-specific-function
#8
Brendan E Russ, Moshe Olshansky, Jasmine Li, Michelle L T Nguyen, Linden J Gearing, Thi H O Nguyen, Matthew R Olson, Hayley A McQuilton, Simone Nüssing, Georges Khoury, Damian F J Purcell, Paul J Hertzog, Sudha Rao, Stephen J Turner
Infection triggers large-scale changes in the phenotype and function of T cells that are critical for immune clearance, yet the gene regulatory mechanisms that control these changes are largely unknown. Using ChIP-seq for specific histone post-translational modifications (PTMs), we mapped the dynamics of ∼25,000 putative CD8+ T cell transcriptional enhancers (TEs) differentially utilized during virus-specific T cell differentiation. Interestingly, we identified a subset of dynamically regulated TEs that exhibited acquisition of a non-canonical (H3K4me3+) chromatin signature upon differentiation...
December 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/29249153/native-and-engineered-clifednamide-biosynthesis-in-multiple-streptomyces-spp
#9
Yunci Qi, Edward Ding, Joshua Blodgett
Polycyclic tetramate macrolactam (PTM) natural products are produced by actinomycetes and other bacteria. PTMs are often bioactive, and the simplicity of their biosynthetic clusters make them attractive for bioengineering. Clifednamide-type PTMs from Streptomyces sp. JV178 contain a distinctive ketone group, suggesting the existence of a novel PTM oxidizing enzyme. Here, we report the new cytochrome P450 enzyme (CftA) is required for clifednamide production. Genome mining was used to identify several new clifednamide producers, some having improved clifednamide yields...
December 18, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29246595/identification-of-post-translational-modifications-of-a%C3%AE-peptide-in-platelet-membranes-from-patients-with-cerebral-amyloid-angiopathy
#10
Lin Song, Rong Xue, Peng Ge, Man Li, Liang Wang, Fang Zheng, Lili Zhao, Zhexiang Wang, Zhuowei Wang, Qianqian Wang, Ning Liu, Xuguo Sun
Cerebral amyloid angiopathy (CAA) is characterized by cerebrovascular amyloid deposition. It contributes to the rate of cognitive decline in older individuals and is present in >90% of patients with Alzheimer's disease (AD), with no cure so far. Molecular modifications during CAA should be elucidated to improve its diagnosis and treatment. In this study, amyloid-β (Aβ) aggregates in platelet membranes from 65 patients with CAA and 66 healthy volunteers (controls) were confirmed through thioflavin T (ThT) assay and Western blot analysis...
December 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29243584/prediction-and-analysis-of-three-dimensional-structure-of-the-p7-transactivated-protein1-of-hepatitis-c-virus
#11
Mahmoud M Elhefnawi, Mohamed E Hasan, Amal Mahmoud, Yehia A Khidr, El-Sayed A El-Absawy, Alaa A Hemeida
BACKGROUND: The p7-transactivated protein of Hepatitis C virus is a small integral membrane protein of 127 amino acids, which is crucial for assembly and release of infectious virions. Ab initio and comparative modelling, is an essential tool to solve the problem of protein structure prediction and to comprehend the physicochemical fundemental of how proteins fold in nature. RESULTS: Only one domain (1-127) of p7 had been predicted using the systematic in silico approach, ThreaDom...
December 15, 2017: Infectious Disorders Drug Targets
https://www.readbyqxmd.com/read/29239840/therapeutic-monoclonal-antibody-n-glycosylation-structure-function-and-therapeutic-potential
#12
REVIEW
Florian Cymer, Hermann Beck, Adelheid Rohde, Dietmar Reusch
Therapeutic antibodies (IgG-type) contain several post-translational modifications (PTMs) whereby introducing a large heterogeneity, both structural and functional, into this class of therapeutics. Of these modifications, glycosylation in the fragment crystallizable (Fc) region is the most heterogeneous PTM, which can affect the stability of the molecule and interactions with Fc-receptors in vivo. Hence, the glycoform distribution can affect the mode of action and have implications for bioactivity, safety and efficacy of the drug...
November 24, 2017: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/29234485/regulation-of-sirtuin-mediated-protein-deacetylation-by-cardioprotective-phytochemicals
#13
REVIEW
Niria Treviño-Saldaña, Gerardo García-Rivas
Modulation of posttranslational modifications (PTMs), such as protein acetylation, is considered a novel therapeutic strategy to combat the development and progression of cardiovascular diseases. Protein hyperacetylation is associated with the development of numerous cardiovascular diseases, including atherosclerosis, hypertension, cardiac hypertrophy, and heart failure. In addition, decreased expression and activity of the deacetylases Sirt1, Sirt3, and Sirt6 have been linked to the development and progression of cardiac dysfunction...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29233872/regulation-of-selective-autophagy-the-p62-sqstm1-paradigm
#14
REVIEW
Trond Lamark, Steingrim Svenning, Terje Johansen
In selective autophagy, cytoplasmic components are selected and tagged before being sequestered into an autophagosome by means of selective autophagy receptors such as p62/SQSTM1. In this review, we discuss how selective autophagy is regulated. An important level of regulation is the selection of proteins or organelles for degradation. Components selected for degradation are tagged, often with ubiquitin, to facilitate recognition by autophagy receptors. Another level of regulation is represented by the autophagy receptors themselves...
December 12, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/29226100/clinical-food-addiction-is-not-associated-with-development-of-metabolic-complications-in-liver-transplant-recipients
#15
Sammy Saab, Cameron Sikavi, Melissa Jimenez, Matthew Viramontes, Ruby Allen, Youssef Challita, Michelle Mai, Negin Esmailzadeh, Jonathan Grotts, Gina Choi, Francisco Durazo, Mohamed El-Kabany, Steven-Huy Han, Elisa Moreno
Background and Aims: Given the increased risk of post-transplant metabolic syndrome (PTMS; defined by hypertension, diabetes mellitus and hyperlipidemia), we aimed to identify the potential role of food addiction in the development of metabolic complications in the post-liver transplant population. Methods: Inclusion criteria included adult liver transplant recipients followed at our institution between June 2016 and November 2016. Participants were administered a demographic survey as well as the Yale Food Assessment Scale 2...
December 28, 2017: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/29226073/cloning-of-canine-ku80-and-its-localization-and-accumulation-at-dna-damage-sites
#16
Manabu Koike, Yasutomo Yutoku, Aki Koike
Molecularly targeted therapies have high specificity and significant cancer-killing effect. However, their antitumor effect might be greatly diminished by variation in even a single amino acid in the target site, as it occurs, for example, as a consequence of SNPs. Increasing evidence suggests that the DNA repair protein Ku80 is an attractive target molecule for the development of next-generation radiosensitizers for human cancers. However, the localization, post-translational modifications (PTMs), and complex formation of Ku80 have not been elucidated in canines...
December 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/29225971/biochemical-analysis-of-histone-succinylation
#17
Atsushi Yokoyama, Shogo Katsura, Akira Sugawara
Posttranslational modification (PTM) of proteins is used to regulate protein activity and stability. Histone PTMs are regarded as some of the most important, as they can directly regulate gene expression through chromatin reorganization. Recently, histone proteins were found to undergo succinylation, adding to other well-known PTMs such as acetylation, methylation, and phosphorylation. However, there is little information regarding the enzyme which catalyzes histone lysine succinylation. In fact, it is unclear whether this reaction is enzymatic...
2017: Biochemistry Research International
https://www.readbyqxmd.com/read/29225593/diverse-cone-snail-species-harbor-closely-related-streptomyces-species-with-conserved-chemical-and-genetic-profiles-including-polycyclic-tetramic-acid-macrolactams
#18
Michelle Quezada, Cuauhtemoc Licona-Cassani, Pablo Cruz-Morales, Angela A Salim, Esteban Marcellin, Robert J Capon, Francisco Barona-Gómez
Streptomyces are Gram-positive bacteria that occupy diverse ecological niches including host-associations with animals and plants. Members of this genus are known for their overwhelming repertoire of natural products, which has been exploited for almost a century as a source of medicines and agrochemicals. Notwithstanding intense scientific and commercial interest in Streptomyces natural products, surprisingly little is known of the intra- and/or inter-species ecological roles played by these metabolites. In this report we describe the chemical structures, biological properties, and biosynthetic relationships between natural products produced by Streptomyces isolated from internal tissues of predatory Conus snails, collected from the Great Barrier Reef, Australia...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29223644/functional-significance-of-o-glcnac-modification-in-regulating-neuronal-properties
#19
REVIEW
Hongik Hwang, Hyewhon Rhim
Post-translational modifications (PTMs) covalently modify proteins and diversify protein functions. Along with protein phosphorylation, another common PTM is the addition of O-linked β-N-acetylglucosamine (O-GlcNAc) to serine and/or threonine residues. O-GlcNAc modification is similar to phosphorylation in that it occurs to serine and threonine residues and cycles on and off with a similar time scale. However, a striking difference is that the addition and removal of the O-GlcNAc moiety on all substrates are mediated by the two enzymes regardless of proteins, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively...
December 6, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29222655/levels-dietary-intake-and-health-risk-of-potentially-toxic-metals-in-vegetables-fruits-and-cereal-crops-in-pakistan
#20
Javed Nawab, Saad Farooqi, Wang Xiaoping, Sardar Khan, Asad Khan
Food safety is a major concern worldwide and human beings are frequently exposed to potentially toxic metals (PTMs) through consumption of vegetables, fruits, and cereal crops grown in contaminated areas. The present study investigates the concentrations of PTMs such as chromium (Cr), nickel (Ni), zinc (Zn), arsenic (As), cadmium (Cd), and lead (Pb) in the foodstuffs (fruits, vegetables, and cereals) collected from different markets of Khyber Pakhtunkhwa, Pakistan. Samples of fruits (banana, tangerine, apple, and guava), vegetables (tomato, onion, potato, pea, and lady finger), and cereals (rice, kidney beans, and chick peas) were acid-extracted and analyzed using ICP-MS...
December 8, 2017: Environmental Science and Pollution Research International
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