scholarly journals Unraveling the Impact of Cysteine-to-Serine Mutations on the Structural and Functional Properties of Cu(I)-Binding Proteins

2019 ◽  
Vol 20 (14) ◽  
pp. 3462 ◽  
Author(s):  
Pavlin ◽  
Qasem ◽  
Sameach ◽  
Gevorkyan-Airapetov ◽  
Ritacco ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Cell Function ◽  
Working Mechanism ◽  
Essential Requirement ◽  
Aggregation Propensity ◽  
Structural And Functional Properties ◽  
Stability Structure ◽  
The Stability ◽  
The Impact ◽  
Partner Proteins

Appropriate maintenance of Cu(I) homeostasis is an essential requirement for proper cell function because its misregulation induces the onset of major human diseases and mortality. For this reason, several research efforts have been devoted to dissecting the inner working mechanism of Cu(I)-binding proteins and transporters. A commonly adopted strategy relies on mutations of cysteine residues, for which Cu(I) has an exquisite complementarity, to serines. Nevertheless, in spite of the similarity between these two amino acids, the structural and functional impact of serine mutations on Cu(I)-binding biomolecules remains unclear. Here, we applied various biochemical and biophysical methods, together with all-atom simulations, to investigate the effect of these mutations on the stability, structure, and aggregation propensity of Cu(I)-binding proteins, as well as their interaction with specific partner proteins. Among Cu(I)-binding biomolecules, we focused on the eukaryotic Atox1-ATP7B system, and the prokaryotic CueR metalloregulator. Our results reveal that proteins containing cysteine-to-serine mutations can still bind Cu(I) ions; however, this alters their stability and aggregation propensity. These results contribute to deciphering the critical biological principles underlying the regulatory mechanism of the in-cell Cu(I) concentration, and provide a basis for interpreting future studies that will take advantage of cysteine-to-serine mutations in Cu(I)-binding systems.

scholarly journals m6A minimally impacts the structure, dynamics, and Rev ARM binding properties of HIV-1 RRE stem IIB

2019 ◽  
Author(s):  
Chia-Chieh Chu ◽  
Bei Liu ◽  
Raphael Plangger ◽  
Christoph Kreutz ◽  
Hashim M. Al-Hashimi
Keyword(s):  
Binding Assays ◽  
Sequence Context ◽  
Rev Response Element ◽  
Stability Structure ◽  
Rna Export ◽  
The Stability ◽  
The Impact ◽  
Melting Experiments ◽  
Hiv 1

AbstractN6-methyladenosine (m6A) is a ubiquitous RNA post-transcriptional modification found in coding as well as non-coding RNAs. m6A has also been found in viral RNAs where it is proposed to modulate host-pathogen interactions. Two m6A sites have been reported in the HIV-1 Rev response element (RRE) stem IIB, one of which was shown to enhance binding to the viral protein Rev and viral RNA export. However, because these m6A sites have not been observed in other studies mapping m6A in HIV-1 RNA, their significance remains to be firmly established. Here, using optical melting experiments, NMR spectroscopy, and in vitro binding assays, we show that m6A minimally impacts the stability, structure, and dynamics of RRE stem IIB as well as its binding affinity to the Rev arginine-rich-motif (ARM). Our results indicate that if present in stem IIB, m6A is unlikely to modulate RRE-Rev interaction by altering the conformational properties of the RNA. Our results add to a growing view that the impact of m6A on RNA depends on sequence context and Mg2+.

Dietary Vitamin and Stability of Oral Anticoagulation: Proposal of a Diet with Constant Vitamin K1 Content

1997 ◽  
Vol 77 (03) ◽  
pp. 504-509 ◽  
Author(s):  
Sarah L Booth ◽  
Jacqueline M Charnley ◽  
James A Sadowski ◽  
Edward Saltzman ◽  
Edwin G Bovill ◽  
...  
Keyword(s):  
Dietary Intake ◽  
Vitamin K ◽  
High Performance ◽  
Case Reports ◽  
Food Composition ◽  
Dietary Guidelines ◽  
Dietary Vitamin ◽  
Vitamin K1 ◽  
The Stability ◽  
The Impact

SummaryCase reports cited in Medline or Biological Abstracts (1966-1996) were reviewed to evaluate the impact of vitamin K1 dietary intake on the stability of anticoagulant control in patients using coumarin derivatives. Reported nutrient-drug interactions cannot always be explained by the vitamin K1 content of the food items. However, metabolic data indicate that a consistent dietary intake of vitamin K is important to attain a daily equilibrium in vitamin K status. We report a diet that provides a stable intake of vitamin K1, equivalent to the current U.S. Recommended Dietary Allowance, using food composition data derived from high-performance liquid chromatography. Inconsistencies in the published literature indicate that prospective clinical studies should be undertaken to clarify the putative dietary vitamin K1-coumarin interaction. The dietary guidelines reported here may be used in such studies.

IMPACT OF GOVERNMENT DEBT ON FINANCIAL SECURITY OF UKRAINE

2017 ◽  
Author(s):  
Olena Pikaliuk ◽  
◽  
Dmitry Kovalenko ◽  
Keyword(s):  
Economic Development ◽  
Public Debt ◽  
Positive Impact ◽  
The State ◽  
Financial Security ◽  
State Budget ◽  
The Public ◽  
Debt Security ◽  
The Stability ◽  
The Impact

One of the main criteria for economic development is the size of the public debt and its dynamics. The article considers the impact of public debt on the financial security of Ukraine. The views of scientists on the essence of public debt and financial security of the state are substantiated. An analysis of the dynamics and structure of public debt of Ukraine for 2014-2019. It is proved that one of the main criteria for economic development is the size of public debt and its dynamics. State budget deficit, attracting and using loans to cover it have led to the formation and significant growth of public debt in Ukraine. The volume of public debt indicates an increase in the debt security of the state, which is a component of financial security. Therefore, the issue of the impact of public debt on the financial security of Ukraine is becoming increasingly relevant. The constant growth and large amounts of debt make it necessary to study it, which will have a positive impact on economic processes that will ensure the stability of the financial system and enhance its security.

Influence of internal and external risks on sustainability of financial system of Аltai krai

2018 ◽  
Vol 35 (4) ◽  
pp. 133-136
Author(s):  
R. N. Ibragimov
Keyword(s):  
Sustainable Development ◽  
Financial Stability ◽  
Management Strategy ◽  
Financial System ◽  
Risk Management Strategy ◽  
The Sustainable Development ◽  
The Stability ◽  
The Impact

The article examines the impact of internal and external risks on the stability of the financial system of the Altai Territory. Classification of internal and external risks of decline, affecting the sustainable development of the financial system, is presented. A risk management strategy is proposed that will allow monitoring of risks, thereby these measures will help reduce the loss of financial stability and ensure the long-term development of the economy of the region.

The Proteins Interacting with Prmt5 in Medaka (Oryzias latipes) Identified by Yeast Two-Hybridization

2020 ◽  
Vol 27 (10) ◽  
pp. 971-978
Author(s):  
Hao Shen ◽  
Xiaosha Zhang ◽  
Md. Abdullah Al Hafiz ◽  
Xiaoting Liang ◽  
Qiting Yao ◽  
...  
Keyword(s):  
Nadh Dehydrogenase ◽  
Binding Proteins ◽  
Zinc Fingers ◽  
Regulation Of Gene Expression ◽  
Apolipoprotein A ◽  
Cell Growth And Differentiation ◽  
Pr Domain ◽  
Partner Proteins ◽  
Apo Ai ◽  
Model Fish

Background: Prmt5 plays major role in regulation of gene expression, RNA processing, cell growth and differentiation, signal transduction, germ cell development, etc., in mammals. Prmt5 is also related to cancer. Knowing the proteins interacting with Prmt5 is important to understand Prmt5’s function in cells. Although there have been reports on proteins binding with Prmt5 in mammals, the partner proteins of Prmt5 in fish are still unclear. Objectives: The objective was to obtain proteins that bind with Prmt5 in medaka, a model fish. Methods: Yeast two hybridization was adopted to achieve the objective. Medaka Prmt5 was used as a bait to fish the prey, binding proteins in a cDNA library of medaka. Co-immunoprecipitation and in silicon analysis were performed to study the interaction of medaka Mep50 and Prmt5. Results: Eight proteins were identified to bind with Prmt5 from 69 preliminary positive colonies. The binding proteins are methylosome protein 50 (Mep50), apolipoprotein A-I-like (Apo-AI), PR domain containing protein 1a with zinc fingers (Prdm1a), Prdm1b, T-cell immunoglobulin mucin family member 3 (Tim-3), phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthase (Paics), NADH dehydrogenase subunit 4 (ND4) and sciellin (Scl). Co-immunoprecipitation confirmed the interaction of medaka Prmt5 and Mep50. Predicted structures of medaka Prtm5 and Mep50 are similar to that of human PRMT5 and MEP50. Conclusion: Medaka Mep50, Prdm1a, Prdm1b, Apo-AI, Tim-3, Paics, ND4, and Scl bind with Prmt5.

Functional characterization and structural modelling of peptidoglycan degrading β-N-acetyl-glucosaminidase from a dental isolate of Serratia marcescens

2020 ◽  
Vol 23 ◽  
Author(s):  
Aditi Rathee ◽  
Anil Panwar ◽  
Seema Kumari ◽  
Sanjay Chhibber ◽  
Ashok Kumar
Keyword(s):  
Functional Characterization ◽  
Major Change ◽  
Crystal Form ◽  
Bound State ◽  
Dynamics Simulation ◽  
Gram Positive ◽  
Structural Cell ◽  
Stability Structure ◽  
Arginine Residues ◽  
The Stability

Introduction:: Enzymatic degradation of peptidoglycan, a structural cell wall component of Gram-positive bacteria, has attracted considerable attention being a specific target for many known antibiotics. Methods:: Peptidoglycan hydrolases are involved in bacterial lysis through peptidoglycan degradation. β-N-acetylglucosaminidase, a peptidoglycan hydrolase, acts on O-glycosidic bonds formed by N-acetylglucosamine and N-acetyl muramic acid residues of peptidoglycan. Aim of present study was to study the action of β-N-acetylglucosaminidase, on methicillin- resistant Staphylococcus aureus (MRSA) and other Gram-negative bacteria. Results:: We investigated its dynamic behaviour using molecular dynamics simulation and observed that serine and alanine residues are involved in catalytic reaction in addition to aspartic acid, histidine, lysine and arginine residues. When simulated in its bound state, the RMSD values were found lesser than crystal form in the time stamp of 1000 picoseconds revealing its stability. Structure remained stably folded over 1000 picoseconds without undergoing any major change further confirming the stability of complex. Conclusion:: It can be concluded that enzymes belonging to this category can serve as a tool in eradicating Gram-positive pathogens and associated infections.

scholarly journals Influence of Whey Protein Micro-Gel Particles and Whey Protein Micro-Gel Particles-Xanthan Gum Complexes on the Stability of O/W Emulsions

Polymers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 2301
Author(s):  
Man Zhang ◽  
Bin Liang ◽  
Hongjun He ◽  
Changjian Ji ◽  
Tingting Cui ◽  
...  
Keyword(s):  
Oxidative Stability ◽  
Whey Protein ◽  
High Speed ◽  
Xanthan Gum ◽  
Physical Stability ◽  
Theoretical Support ◽  
Gel Particles ◽  
Oil In Water ◽  
The Stability ◽  
The Impact

Appropriate pretreatment of proteins and addition of xanthan gum (XG) has the potential to improve the stability of oil-in-water (O/W) emulsions. However, the factors that regulate the enhancement and the mechanism are still not clear, which restricts the realization of improving the emulsion stability by directional design of its structure. Therefore, the effects of whey protein micro-gel particles (WPMPs) and WPMPs-XG complexes on the stability of O/W emulsion were investigated in this article to provide theoretical support. WPMPs with different structures were prepared by pretreatment (controlled high-speed shear treatment of heat-set WPC gels) at pH 3.5–8.5. The impact of initial WPC structure and XG addition on Turbiscan Indexes, mean droplet size and the peroxide values of O/W emulsions was investigated. The results indicate that WPMPs and XG can respectively inhibit droplet coalescence and gravitational separation to improve the physical stability of WPC-stabilized O/W emulsions. The pretreatment significantly enhanced the oxidative stability of WPC-stabilized O/W emulsions. The addition of XG did not necessarily enhance the oxidative stability of O/W emulsions. Whether the oxidative stability of the O/W emulsion with XG is increased or decreased depends on the interface structure of the protein-XG complex. This study has significant implications for the development of novel structures containing lipid phases that are susceptible to oxidation.

scholarly journals Post-Processing Techniques for the Improvement of Liposome Stability

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1023
Author(s):  
Ji Young Yu ◽  
Piyanan Chuesiang ◽  
Gye Hwa Shin ◽  
Hyun Jin Park
Keyword(s):  
Freeze Drying ◽  
Protective Agent ◽  
Post Processing ◽  
Additional Process ◽  
Spray Freeze Drying ◽  
The Stability ◽  
Processing Techniques ◽  
The Impact ◽  
Self Aggregation ◽  
Liposome Stability

Liposomes have been utilized as a drug delivery system to increase the bioavailability of drugs and to control the rate of drug release at the target site of action. However, the occurrence of self-aggregation, coalescence, flocculation and the precipitation of aqueous liposomes during formulation or storage can cause degradation of the vesicle structure, leading to the decomposition of liposomes. To increase the stability of liposomes, post-processing techniques have been applied as an additional process to liposomes after formulation to remove water and generate dry liposome particles with a higher stability and greater accessibility for drug administration in comparison with aqueous liposomes. This review covers the effect of these techniques including freeze drying, spray drying and spray freeze drying on the stability, physicochemical properties and drug encapsulation efficiency of dry liposomes. The parameters affecting the properties of liposomes during the drying process are also highlighted in this review. In addition, the impact of using a protective agent to overcome such limitations of each process is thoroughly discussed through various studies.

scholarly journals Dynamics of the rumor-spreading model with hesitation mechanism in heterogenous networks and bilingual environment

2020 ◽  
Vol 2020 (1) ◽  
Author(s):  
Shuai Yang ◽  
Haijun Jiang ◽  
Cheng Hu ◽  
Juan Yu ◽  
Jiarong Li
Keyword(s):  
Lyapunov Method ◽  
Reproduction Number ◽  
Model Parameters ◽  
Rumor Spreading ◽  
Spreading Model ◽  
Reductio Ad Absurdum ◽  
The Stability ◽  
The Impact ◽  
Theoretical Results ◽  
The Basic Reproduction Number

Abstract In this paper, a novel rumor-spreading model is proposed under bilingual environment and heterogenous networks, which considers that exposures may be converted to spreaders or stiflers at a set rate. Firstly, the nonnegativity and boundedness of the solution for rumor-spreading model are proved by reductio ad absurdum. Secondly, both the basic reproduction number and the stability of the rumor-free equilibrium are systematically discussed. Whereafter, the global stability of rumor-prevailing equilibrium is explored by utilizing Lyapunov method and LaSalle’s invariance principle. Finally, the sensitivity analysis and the numerical simulation are respectively presented to analyze the impact of model parameters and illustrate the validity of theoretical results.

scholarly journals The influence of density in population dynamics with strong and weak Allee effect

2021 ◽  
Vol 29 (1) ◽  
Author(s):  
Kamrun Nahar Keya ◽  
Md. Kamrujjaman ◽  
Md. Shafiqul Islam
Keyword(s):  
Population Dynamics ◽  
Allee Effect ◽  
Global Bifurcation ◽  
Reaction Diffusion ◽  
Logistic Growth ◽  
Allee Effects ◽  
Reaction Diffusion Model ◽  
Positive Steady States ◽  
The Stability ◽  
The Impact

AbstractIn this paper, we consider a reaction–diffusion model in population dynamics and study the impact of different types of Allee effects with logistic growth in the heterogeneous closed region. For strong Allee effects, usually, species unconditionally die out and an extinction-survival situation occurs when the effect is weak according to the resource and sparse functions. In particular, we study the impact of the multiplicative Allee effect in classical diffusion when the sparsity is either positive or negative. Negative sparsity implies a weak Allee effect, and the population survives in some domain and diverges otherwise. Positive sparsity gives a strong Allee effect, and the population extinct without any condition. The influence of Allee effects on the existence and persistence of positive steady states as well as global bifurcation diagrams is presented. The method of sub-super solutions is used for analyzing equations. The stability conditions and the region of positive solutions (multiple solutions may exist) are presented. When the diffusion is absent, we consider the model with and without harvesting, which are initial value problems (IVPs) and study the local stability analysis and present bifurcation analysis. We present a number of numerical examples to verify analytical results.

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