A comprehensive overview of PPM1A: From structure to disease

PPM1A (magnesium-dependent phosphatase 1 A, also known as PP2Cα) is a member of the Ser/Thr protein phosphatase family. Protein phosphatases catalyze the removal of phosphate groups from proteins via hydrolysis, thus opposing the role of protein kinases. The PP2C family is generally considered a negative regulator in the eukaryotic stress response pathway. PPM1A can bind and dephosphorylate various proteins and is therefore involved in the regulation of a wide range of physiological processes. It plays a crucial role in transcriptional regulation, cell proliferation, and apoptosis and has been suggested to be closely related to the occurrence and development of cancers of the lung, bladder, and breast, amongst others. Moreover, it is closely related to certain autoimmune diseases and neurodegenerative diseases. In this review, we provide an insight into currently available knowledge of PPM1A, including its structure, biological function, involvement in signaling pathways, and association with diseases. Lastly, we discuss whether PPM1A could be targeted for therapy of certain human conditions.

Synthesis and Characterization of Polyurethanes from Residual Palm Oil with High Poly-Unsaturated Fatty Acid Oils as Additive

In the effort to produce renewable and biodegradable polymers, more studies are being undertaken to explore environmentally friendly sources to replace petroleum-based sources. The oil palm industry is not only the biggest vegetable-oil producer from crops but also one the biggest producers of residual oil that cannot be used for edible purposes due to its low quality. In this paper the development of biopolymers from residual palm oil, residual palm oil with 10% jatropha oil, and residual palm oil with 10% algae oil as additives were explored. Polyols from the different oils were prepared by epoxydation with peroxyacetic acid and alcoholysis under the same conditions and further reacted with poly isocyanate to form polyurethanes. Epoxidized oils, polyols and polyurethanes were analyzed by different techniques such as TGA, DSC, DMA, FTIR and H-NMR. Overall, although the IV of algae oil is slightly higher than that of jatropha oil, the usage of algae oil as additive into the residual palm oil was shown to significantly increase the hard segments and thermal stability of the bio polyurethane compared to the polymer with jatropha oil. Furthermore, when algae oil was mixed with the residual palm oil, it was possible to identify phosphate groups in the polyol which might enhance the fire-retardant properties of the final biopolymer.

Recent Trends in rationally designed molecules as kinase inhibitors

: Protein kinases modulate the structure and function of proteins by adding phosphate groups to threonine, tyrosine, and serine residues. The phosphorylation process mediated by the kinases regulates several physiological processes, while their overexpression results in the development of chronic diseases, including cancer. Targeting of receptor tyrosine kinase pathways results in the inhibition of angiogenesis and cell proliferation that validates kinases as a key target in the management of aggressive cancers. As such, the identification of protein kinase inhibitors revolutionized the contemporary anticancer therapy by inducing a paradigm shift in the management of disease pathogenesis. Contemporary drug design programs focus on a broad range of kinase targets for the development of novel pharmacophores to manage the overexpression of kinases and their pathophysiology in cancer pathogenesis. In this review, we present the emerging trends in the development of rationally designed molecular inhibitors of kinases over the last five years (2016-2021) and their incipient role in the development of impending anticancer pharmaceuticals.

Kinetic and Interaction Studies of Adenosine-5′-Triphosphate (ATP) Hydrolysis with Polyoxovanadates

The reactivity of polyoxovanadates towards adenosine-5′-triphosphate (ATP) hydrolysis at pH 2, 4, 6 and 7 is reported. Detailed kinetic investigation of ATP hydrolysis in the presence of polyoxovanadates was performed through multinuclear nuclear magnetic resonance (NMR) spectroscopy. In general, rate acceleration of up to five orders of magnitude was observed in the presence of vanadates compared to spontaneous ATP hydrolysis, with the greatest acceleration observed for reactions carried out at pH 2. Interestingly, the effectiveness of vanadates in promoting ATP hydrolysis decreased as the pH of the reaction solution increased; nevertheless, at pH = 7, the rate increase of one order of magnitude in comparison to blank reactions was still observed. Interactions between vanadate species in solution and ATP were investigated by means of 31P and 51V NMR spectroscopy, and this pointed towards the preferential interaction of vanadium with the phosphate groups rather than other regions of the ATP molecule.

The DNA Recognition Motif of GapR Has an Intrinsic DNA Binding Preference towards AT-rich DNA

The nucleoid-associated protein GapR found in Caulobacter crescentus is crucial for DNA replication, transcription, and cell division. Associated with overtwisted DNA in front of replication forks and the 3′ end of highly-expressed genes, GapR can stimulate gyrase and topo IV to relax (+) supercoils, thus facilitating the movement of the replication and transcription machines. GapR forms a dimer-of-dimers structure in solution that can exist in either an open or a closed conformation. It initially binds DNA through the open conformation and then undergoes structural rearrangement to form a closed tetramer, with DNA wrapped in the central channel. Here, we show that the DNA binding domain of GapR (residues 1–72, GapRΔC17) exists as a dimer in solution and adopts the same fold as the two dimer units in the full-length tetrameric protein. It binds DNA at the minor groove and reads the spatial distribution of DNA phosphate groups through a lysine/arginine network, with a preference towards AT-rich overtwisted DNA. These findings indicate that the dimer unit of GapR has an intrinsic DNA binding preference. Thus, at the initial binding step, the open tetramer of GapR with two relatively independent dimer units can be more efficiently recruited to overtwisted regions.

Analysis of Cr(III) ions adsorption on the surface of algae: implications for the removal of heavy metal ions from water

For purposeful control of the adsorption process, a comprehensive study of the properties of the original cells and the effect of metal ions on them is necessary. In this regard, the features of the adsorption of Cr(III) ions on the cell surface of Spirulina platensis algae were studied. FTIR spectroscopy revealed that the main functional groups responsible for the binding of Cr(III) ions are carboxyl, hydroxyl, amino, and phosphate groups on the surface of algae. The adsorption data were processed using the Langmuir and Freundlich models. It is shown that the maximum adsorption of Cr(III) ions on the surface of algae cells is 31.25 mg/g. The Freundlich constant 1/n is 0.65. The study of the effect of the concentration of Cr(III) ions on the Zeta-potential of algae cells revealed an abnormal increase in the negative value of the ζ – potential at 10–5 mol/L, caused by the release of an additional amount of anionic functional groups to the surface. A further increase in the concentration of Cr(III) ions in the algae suspension leads to a decrease in the ζ – potential and recharge of the surface at C>10–2 mol/L. It was found that the adsorption of Cr(III) ions also affects the morphology of the cell surface. If before contact with Cr(III) ions, the surface of algae cells is represented as a uniform green grid, after adsorption of Cr(III) ions, the surface becomes green-brown, with swollen spirals. The study of the effect of pH on the adsorption and desorption processes shows an increase in the desorption of Cr(III) ions from the surface of algae during acidification of the medium. The adsorption reaches a maximum value in the pH range of 6–7. In the region of optimal Cr(III)/biosorbent ion ratios, the recovery rate of Cr(III) reaches 98.5–99.3 %.

Uncharged Components of Single-Stranded DNA Modulate Liquid–Liquid Phase Separation With Cationic Linker Histone H1

Liquid–liquid phase separation (LLPS) of proteins and DNAs has been recognized as a fundamental mechanism for the formation of intracellular biomolecular condensates. Here, we show the role of the constituent DNA components, i.e., the phosphate groups, deoxyribose sugars, and nucleobases, in LLPS with a polycationic peptide, linker histone H1, a known key regulator of chromatin condensation. A comparison of the phase behavior of mixtures of H1 and single-stranded DNA-based oligomers in which one or more of the constituent moieties of DNA were removed demonstrated that not only the electrostatic interactions between the anionic phosphate groups of the oligomers and the cationic residues of H1, but also the interactions involving nucleobases and deoxyriboses (i) promoted the generation of spherical liquid droplets via LLPS as well as (ii) increased the density of DNA and decreased its fluidity within the droplets under low-salt conditions. Furthermore, we found the formation of non-spherical assemblies with both mobile and immobile fractions at relatively higher concentrations of H1 for all the oligomers. The roles of the DNA components that promote phase separation and modulate droplet characteristics revealed in this study will facilitate our understanding of the formation processes of the various biomolecular condensates containing nucleic acids, such as chromatin organization.