Data on the role of accessible surface area on osmolytes-induced protein stabilization

AbstractThis paper describes data related to the research article “Testing the dependence of stabilizing effect of osmolytes on the fractional increase in the accessible surface area on thermal and chemical denaturations of proteins” [1]. Heat- and guanidinium chloride (GdmCl)-induced denaturation of three disulfide free proteins (bovine cytochrome c (b-cyt-c), myoglobin (Mb) and barstar) in the presence of different concentrations of methylamines (sarcosine, glycine-betaine (GB) and trimethylamine-N-oxide (TMAO)) was monitored by [ϴ]222, the mean residue ellipticity at 222nm at pH 7.0. Methylamines belong to a class of osmolytes known to protect proteins from deleterious effect of urea. This paper includes comprehensive thermodynamic data obtained from the heat- and GdmCl-induced denaturations of barstar, b-cyt-c and Mb

Co-infection with Dengue and Chikungunya Viruses

Dengue and Chikungunya fever are the arboviral infections that are endemic in tropical and subtropical regions. These two viral infections share common clinical symptoms. These infections are transmitted by a common mosquito vector so these viruses co-circulate in many geographical regions. Various clinical investigations, particularly from India and African countries have documented the dual infection with these viruses. However, the true disease burden of Dengue and Chikungunya dual viral infections is still not known because most of these studies involved a smaller patient group. Therefore, in depth investigations involving larger patient groups are needed to examine the complete pathogenicity and severity of the dual viral infections. The timely diagnosis of the pathogens and correlation of disease severity with mono or dual infections is essential for effective patient management. In addition, the detailed molecular and cellular mechanism of co-infection should be investigated to describe a complete picture of the interaction of two viral pathogens in the host cell. Further comprehensive studies of dual infections from the endemic regions will determine the epidemiological and evolutionary pattern of these emerging viruses. This data will also assist in designing and implementation of effective control measures

Antibiotic adjuvants: synergistic tool to combat multi-drug resistant pathogens

The rise of multi-drug resistant (MDR) pathogens poses a significant challenge to the field of infectious disease treatment. To overcome this problem, novel strategies are being explored to enhance the effectiveness of antibiotics. Antibiotic adjuvants have emerged as a promising approach to combat MDR pathogens by acting synergistically with antibiotics. This review focuses on the role of antibiotic adjuvants as a synergistic tool in the fight against MDR pathogens. Adjuvants refer to compounds or agents that enhance the activity of antibiotics, either by potentiating their effects or by targeting the mechanisms of antibiotic resistance. The utilization of antibiotic adjuvants offers several advantages. Firstly, they can restore the effectiveness of existing antibiotics against resistant strains. Adjuvants can inhibit the mechanisms that confer resistance, making the pathogens susceptible to the action of antibiotics. Secondly, adjuvants can enhance the activity of antibiotics by improving their penetration into bacterial cells, increasing their stability, or inhibiting efflux pumps that expel antibiotics from bacterial cells. Various types of antibiotic adjuvants have been investigated, including efflux pump inhibitors, resistance-modifying agents, and compounds that disrupt bacterial biofilms. These adjuvants can act synergistically with antibiotics, resulting in increased antibacterial activity and overcoming resistance mechanisms. In conclusion, antibiotic adjuvants have the potential to revolutionize the treatment of MDR pathogens. By enhancing the efficacy of antibiotics, adjuvants offer a promising strategy to combat the growing threat of antibiotic resistance. Further research and development in this field are crucial to harness the full potential of antibiotic adjuvants and bring them closer to clinical application

Interferons Horizon Therapeutics

Interferons (IFNs) are a family of multi-functional proteins, called cytokines, that are produced by immune cells such as leukocytes, natural killer (NK) cells, macrophages, fibroblasts, and epithelial cells. The minute amount of these α-helical glycoproteins, produced by mammalian cells, are firm components of the innate arm of the immune system providing rapid and broad protection against numerous types of invading pathogens. Interferons, from their discovery in the 19th century, have always held out a promise of important clinical utility first as an antiviral agent and more recently holding anti-inflammatory and regenerative effects for treating various neurological diseases such as multiple sclerosis, encephalopathies, Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), etc. IFNs elicit anti-viral and anti-inflammatory properties by inducing transcription of multiple IFN stimulated genes (ISG), a response that is partly mediated by Interferon regulatory factors (IRFs). This chapter provides a brief introduction of the interferon system as well as an in-depth assessment of the interferon signature and the various assay procedures for synthesizing non-natural interferon analogs for structural analysis, which may be helpful in designing improved products and act as a diagnostic tool for neurodegenerative disorders

Insights into Fluctuations of Structure of Proteins: Significance of Intermediary States in Regulating Biological Functions

Proteins are indispensable to cellular communication and metabolism. The structure on which cells and tissues are developed is deciphered from proteins. To perform functions, proteins fold into a three-dimensional structural design, which is specific and fundamentally determined by their characteristic sequence of amino acids. Few of them have structural versatility, allowing them to adapt their shape to the task at hand. The intermediate states appear momentarily, while protein folds from denatured (D) ⇔ native (N), which plays significant roles in cellular functions. Prolific effort needs to be taken in characterizing these intermediate species if detected during the folding process. Protein folds into its native structure through definite pathways, which involve a limited number of transitory intermediates. Intermediates may be essential in protein folding pathways and assembly in some cases, as well as misfolding and aggregation folding pathways. These intermediate states help to understand the machinery of proper folding in proteins. In this review article, we highlight the various intermediate states observed and characterized so far under in vitro conditions. Moreover, the role and significance of intermediates in regulating the biological function of cells are discussed clearly

Insights into Fluctuations of Structure of Proteins: Significance of Intermediary States in Regulating Biological Functions

Proteins are indispensable to cellular communication and metabolism. The structure on which cells and tissues are developed is deciphered from proteins. To perform functions, proteins fold into a three-dimensional structural design, which is specific and fundamentally determined by their characteristic sequence of amino acids. Few of them have structural versatility, allowing them to adapt their shape to the task at hand. The intermediate states appear momentarily, while protein folds from denatured (D) ⇔ native (N), which plays significant roles in cellular functions. Prolific effort needs to be taken in characterizing these intermediate species if detected during the folding process. Protein folds into its native structure through definite pathways, which involve a limited number of transitory intermediates. Intermediates may be essential in protein folding pathways and assembly in some cases, as well as misfolding and aggregation folding pathways. These intermediate states help to understand the machinery of proper folding in proteins. In this review article, we highlight the various intermediate states observed and characterized so far under in vitro conditions. Moreover, the role and significance of intermediates in regulating the biological function of cells are discussed clearly

Interaction of fungal lipase with potential phytotherapeutics.

Interaction of thymol, carvacrol and linalool with fungal lipase and Human Serum Albumin (HSA) have been investigated employing UV-Vis spectroscopy Fluorescence and Circular dichroism spectroscopy (CD) along with docking studies. Thymol, carvacrol and linalool displayed approximately 50% inhibition at 1.5 mmol/litre concentrations using para-nitrophenyl palmitate (pNPP). UV-Vis spectroscopy give evidence of the formation of lipase-linalool, lipase-carvacrol and lipase-thymol complex at the ground state. Three molecules also showed complex formation with HSA at the ground state. Fluorescence spectroscopy shows strong binding of lipase to thymol (Ka of 2.6 x 109 M-1) as compared to carvacrol (4.66 x 107 M-1) and linalool (5.3 x 103 M-1). Number of binding sites showing stoichiometry of association process on lipase is found to be 2.52 (thymol) compared to 2.04 (carvacrol) and 1.12 (linalool). Secondary structure analysis by CD spectroscopy results, following 24 hours incubation at 25°C, with thymol, carvacrol and linalool revealed decrease in negative ellipticity for lipase indicating loss in helical structure as compared with the native protein. The lowering in negative ellipticity was in the order of thymol > carvacrol > linalool. Fluorescence spectra following binding of all three molecules with HSA caused blue shift which suggests the compaction of the HSA structure. Association constant of thymol and HSA is 9.6 x 108 M-1 which along with 'n' value of 2.41 suggests strong association and stable complex formation, association constant for carvacrol and linalool was in range of 107 and 103 respectively. Docking results give further insight into strong binding of thymol, carvacrol and linalool with lipase having free energy of binding as -7.1 kcal/mol, -5.0 kcal/mol and -5.2 kcal/mol respectively. To conclude, fungal lipases can be attractive target for controlling their growth and pathogenicity. Employing UV-Vis, Fluorescence and Circular dichroism spectroscopy we have shown that thymol, carvacrol and linalool strongly bind and disrupt structure of fungal lipase, these three phytochemicals also bind well with HSA. Based on disruption of lipase structure and its binding nature with HSA, we concluded thymol as a best anti-lipase molecule among three molecules tested. Results of Fluorescence and CD spectroscopy taken together suggests that thymol and carvacrol are profound disrupter of lipase structure

Role of unique basic residues of human pancreatic ribonuclease in its catalysis and structural stability

Human pancreatic ribonuclease (HPR) and bovine RNase A belong to the RNase A superfamily and possess similar key structural and catalytic residues. Compared to RNase A, HPR has six extra non-catalytic basic residues and high double-stranded RNA (dsRNA) cleavage activity. We mutated four of these basic residues, K6, R32, K62, and K74 to alanine and characterized the variants for function and stability. Only the variant K74A had an altered secondary structure. Whereas R32A and K62A had full catalytic activity, the mutants K6A and K74A had reduced activity on both ssRNA and dsRNA. The mutations of K62 and K74 resulted in reduction in protein stability and DNA double helix unwinding activity of HPR; while substitutions of K6 and R32 did not affect either the stability or helix unwinding activity. The reduced catalytic and DNA melting activities of K74A mutant appear to be an outcome of its altered secondary structure. The basic residues studied here, appear to contribute to the overall stability, folding, and general catalytic activity of HPR

Human Disease Insight: An integrated knowledge-based platform for disease-gene-drug information

Summary: The scope of the Human Disease Insight (HDI) database is not limited to researchers or physicians as it also provides basic information to non-professionals and creates disease awareness, thereby reducing the chances of patient suffering due to ignorance. HDI is a knowledge-based resource providing information on human diseases to both scientists and the general public. Here, our mission is to provide a comprehensive human disease database containing most of the available useful information, with extensive cross-referencing. HDI is a knowledge management system that acts as a central hub to access information about human diseases and associated drugs and genes. In addition, HDI contains well-classified bioinformatics tools with helpful descriptions. These integrated bioinformatics tools enable researchers to annotate disease-specific genes and perform protein analysis, search for biomarkers and identify potential vaccine candidates. Eventually, these tools will facilitate the analysis of disease-associated data. The HDI provides two types of search capabilities and includes provisions for downloading, uploading and searching disease/gene/drug-related information. The logistical design of the HDI allows for regular updating. The database is designed to work best with Mozilla Firefox and Google Chrome and is freely accessible at http://humandiseaseinsight.com. Keywords: Human disease database, Human genome project, Data integration, Knowledge management system, Relational database management syste