Chromatin is a dynamic DNA scaffold structure that responds to a variety of external and internal stimuli to regulate the fundamental biological processes. Majority of the cases chromatin dynamicity ...is exhibited through chemical modifications and physical changes between DNA and histones. These modifications are reversible and complex signaling pathways involving chromatin-modifying enzymes regulate the fluidity of chromatin. Fluidity of chromatin can also be impacted through irreversible change, proteolytic processing of histones which is a poorly understood phenomenon. In recent studies, histone proteolysis has been implicated as a regulatory process involved in the permanent removal of epigenetic marks from histones. Activities responsible for clipping of histone tails and their significance in various biological processes have been observed in several organisms. Here, we have reviewed the properties of some of the known histone proteases, analyzed their significance in biological processes and have provided future directions.
Histone H3 N-terminal tail (H3NT) clipping has been known for the last four decades, but its functional significance is still poorly understood. H3NT clipping has never received proper attention ...because it was thought that clipping is the result of the non-specific action of cellular proteases. However, in the last few years, several histone-specific proteases have been identified, and their functions have started to unravel. This paper discusses the recently identified H3-specific proteases, the consequences of histone clipping, and future perspectives.
Ebselen, an organoselenium compound, mimics glutathione peroxidase activity. It is a multifunctional compound, which catalyzes several essential reactions for the protection of cellular components ...from oxidative and free radical damage. Based on a number of in vitro and in vivo studies, various mechanisms are proposed to understand the biomedical actions of ebselen in health and diseases. It modulates metallo-proteins, enzymatic cofactors, gene expression, epigenetics, antioxidant defenses and immune systems. Owing to these properties, ebselen is currently under clinical trials for the prevention and treatment of various disorders such as cardiovascular diseases, arthritis, stroke, atherosclerosis, and cancer. A few ebselen-based pharmaceutical agents are under extensive investigation. As ebselen has been shown to have significant cellular toxicity, appropriate studies are needed to redesign the ebselen-based therapy for clinical trials. This review summarizes current understanding of the biochemical and molecular properties, and pharmacological applications of ebselen and future directions in this area of research.
Coronavirus disease- 2019 (COVID-19) has rapidly become a major threat to humans due to its high infection rate and deaths caused worldwide. This disease is caused by an RNA virus, Severe Acquired ...Respiratory Syndrome –Corona Virus-2 (SARS-CoV-2). This class of viruses have a high rate of mutation than DNA viruses that enables them to adapt and also evade host immune system. Here, we compared the first known Nucleocapsid Phosphoprotein (N protein) sequence of SARS-CoV-2 from China with the sequences from Indian COVID-19 patients to understand, if this virus is also mutating, as it is spreading to new locations. Our data revealed twenty mutations present among Indian isolates. Out of these, mutation at six positions led to changes in the secondary structure of N protein. Further, we also show that these mutations are primarily destabilising the protein structure. The candidate mutations identified in this study may help to speed up the understanding of variations occurring in SARS-CoV-2.
COVID-19; SARS-CoV-2; Mutations; Nucleocapsid Phosphoprotein (N); Infectious diseases; India
The highly conserved protein kinase TOR and its signaling network controls cell growth in response to nutrients, growth factors, and other environmental conditions 23. The corresponding author noted ...that Sml1 degradation in response to DNA damage is a well-known phenomenon and following consultation with a PLOS ONE Editorial Board Member, this issue is considered resolved. The corresponding author stated that the original, uncropped images underlying this article 1 are partly available for Figs 1, 3, 4 and 5, and that the individual-level quantitative data underlying this article 1 are available for Figs 1A, 1C and 4A.
A recent outburst of the pandemic caused by a member of the coronaviridae family identified as SARS-CoV-2. The highly contagious nature of the virus allows it to spread rapidly worldwide and caused ...severe healthcare and economic distress. So far, no proper line of treatment or vaccines has been available against SARS-CoV-2. Since, the infected people rapidly increased, causing the saturation of healthcare systems with coronavirus disease (COVID-19) patients. As the virus spread to new locations it also acquired various mutations. Here, in this study, we focused on identifying mutations in one of the crucial complex of SARS-CoV-2, the Nsp10-Nsp16 2′-O-methyltransferase complex. This complex plays indispensable role in the post-transcriptional modifications of viral RNA by its capping. We analysed 208 sequences of Nsp10-Nsp16 reported from India and compared with first reported sequence from Wuhan, China. Our analysis revealed a single mutation in Nsp10 and five mutations in Nsp16 protein. We also show that these mutations are leading to alteration in the secondary structure of Nsp10-Nsp16. Further, the protein modelling studies revealed that the mutation of both Nsp10-Nsp16 impacts the protein dynamicity and stability. Altogether, this study provides novel insights into the variations observed in the proteins of SARS-CoV-2 that might have functional consequences.
•The non-structural protein of SARS-CoV-2, Nsp 10 and Nsp16 is mutated as it spreads to new locations.•SARS-CoV-2 harbours six mutations in Nsp 10-Nsp16 complex among Indian Isolates.•These mutation alters secondary structure of both Nsp 10 and Nsp16 and also affects protein dynamicity.
The rapid development of the SARS-CoV-2 mediated COVID-19 pandemic has been the cause of significant health concern, highlighting the immediate need for effective antivirals. SARS-CoV-2 is an RNA ...virus that has an inherently high mutation rate. These mutations drive viral evolution and genome variability, thereby facilitating viruses to have rapid antigenic shifting to evade host immunity and to develop drug resistance. Viral RNA-dependent RNA polymerases (RdRp) perform viral genome duplication and RNA synthesis. Therefore, we compared the available RdRp sequences of SARS-CoV-2 from Indian isolates and the ‘Wuhan wet sea food market virus’ sequence to identify, if any, variation between them. Our data revealed the occurrence of seven mutations in Indian isolates of SARS-CoV-2. The secondary structure prediction analysis of these seven mutations shows that three of them cause alteration in the structure of RdRp. Furthermore, we did protein modelling studies to show that these mutations can potentially alter the stability of the RdRp protein. Therefore, we propose that RdRp mutations in Indian SARS-CoV-2 isolates might have functional consequences that can interfere with RdRp targeting pharmacological agents.
The development of a water oxidation catalyst has been a demanding challenge in realizing water splitting systems. The asymmetric geometry and flexible ligation of the biological Mn4CaO5 cluster are ...important properties for the function of photosystem II, and these properties can be applied to the design of new inorganic water oxidation catalysts. We identified a new crystal structure, Mn3(PO4)2·3H2O, that precipitates spontaneously in aqueous solution at room temperature and demonstrated its high catalytic performance under neutral conditions. The bulky phosphate polyhedron induces a less-ordered Mn geometry in Mn3(PO4)2·3H2O. Computational analysis indicated that the structural flexibility in Mn3(PO4)2·3H2O could stabilize the Jahn–Teller-distorted Mn(III) and thus facilitate Mn(II) oxidation. This study provides valuable insights into the interplay between atomic structure and catalytic activity.
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•System thermodynamics of the antisolvent crystallization is discussed.•Supersaturation, MSZW, induction time, crystallization kinetics are critically analysed.•Hydrodynamic modeling ...and CFD-based approach for LASC are critically reviewed.•A complete outlook of LASC is presented.•Modeling based LASC scale-up guidelines and challenges are discussed.
Fine particles are in great demand in the pharmaceutical industry due to their versatile applications. Liquid antisolvent crystallization (LASC) is one of the promising approaches to prepare fine particles without requiring high energy. The interdependence of system thermodynamics, mass transfer kinetics, and the multi-phase hydrodynamics in the liquid antisolvent crystallization process is not well understood. In this review, the different modeling aspects of LASC are described from a fundamental perspective. The system thermodynamics of LASC is discussed and several models used in literature to predict the solubility in pure solvents and binary solvent mixtures are summarized. A detailed description of supersaturation, metastable zone width and induction time in antisolvent crystallization are presented and critically analyzed. The nucleation and growth kinetics are discussed and interpreted in terms of process variables. The hydrodynamic aspect of LASC which involves the mixing at different length scales is discussed and analyzed in detail. The CFD simulation-based approach to describe the interaction among different phenomena is critically reviewed. The crystallization scale-up, which is a major challenge in the LASC process, is discussed. A guideline for crystallization scale-up using the CFD-based modeling approach is presented which will be helpful to prospective researchers.
Severe acquired respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread worldwide and acquired multiple mutations in its genome. Orf3a, an accessory protein encoded by the genome of ...SARS-CoV-2, plays a significant role in viral infection and pathogenesis. In the present in-silico study, 15,928 sequences of Orf3a reported worldwide were compared to identify variations in this protein. Our analysis revealed the occurrence of mutations at 173 residues of Orf3a protein. Subsequently, protein modelling was performed that revealed twelve mutations which can considerably affect the stability of Orf3a. Among the 12 mutations, three mutations (Y160H, D210Y and S171L) also lead to alterations in secondary structure and protein disorder parameters of the Orf3a protein. Further, we used predictive tools to identify five promising epitopes of B-cells, which resides in the mutated regions of Orf3a. Altogether, our study sheds light on the variations occurring in Orf3a that might contribute to alteration in protein structure and function.
•The Open reading frame 3a (Orf3a) protein acquired mutations as it spread to new locations.•The Orf3a protein harbours 173 mutations.•These mutation alters secondary structure, protein disorder parameters and also affects Orf3a protein dynamicity.•The high rank B-cell epitopes resides in the mutated regions of Orf3a that might help the virus to evade immune system.
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