Selenomethionine Incorporation into Amyloid Sequences Regulates Fibrillogenesis and Toxicity

The capacity of a polypeptide chain to engage in an amyloid formation process and cause a conformational disease is contained in its sequence. Some of the sequences undergoing fibrillation contain critical methionine (Met) residues which in vivo can be synthetically substituted by selenomethionine (SeM) and alter their properties

Dimer Formation Enhances Structural Differences between Amyloid β-Protein (1–40) and (1–42): An Explicit-Solvent Molecular Dynamics Study

Amyloid -protein (A) is central to the pathology of Alzheimer's disease. A 5% difference in the primary structure of the two predominant alloforms, A and A, results in distinct assembly pathways and toxicity properties. Discrete molecular dynamics (DMD) studies of A and A assembly resulted in alloform-specific oligomer size distributions consistent with experimental findings. Here, a large ensemble of DMD–derived A and A monomers and dimers was subjected to fully atomistic molecular dynamics (MD) simulations using the OPLS-AA force field combined with two water models, SPCE and TIP3P. The resulting all-atom conformations were slightly larger, less compact, had similar turn and lower -strand propensities than those predicted by DMD. Fully atomistic A and A monomers populated qualitatively similar free energy landscapes. In contrast, the free energy landscape of A dimers indicated a larger conformational variability in comparison to that of A dimers. A dimers were characterized by an increased flexibility in the N-terminal region D1-R5 and a larger solvent exposure of charged amino acids relative to A dimers. Of the three positively charged amino acids, R5 was the most and K16 the least involved in salt bridge formation. This result was independent of the water model, alloform, and assembly state. Overall, salt bridge propensities increased upon dimer formation. An exception was the salt bridge propensity of K28, which decreased upon formation of A dimers and was significantly lower than in A dimers. The potential relevance of the three positively charged amino acids in mediating the A oligomer toxicity is discussed in the light of available experimental data

Interaction of two imidazolium gemini surfactants with two model proteins BSA and HEWL

Gemini surfactants and their interactions with proteins have gained considerable scientific interest, especially when amyloidogenic proteins are taken into account. In this work, the influence of two selected dicationic (gemini) surfactants (3,3′-[1,8-(2,7-dioxaoctane)]bis(1-dodecylimidazolium) chloride and 3,3′-[1,12-(2,11-dioxadodecane)]bis(1-dodecylimidazolium) chloride) on two model proteins, bovine serum albumin (BSA) and hen egg white lysozyme (HEWL), have been investigated. A pronounced and sophisticated influence on BSA structure has been revealed, including a considerable change of protein radius of gyration as well as substantial alteration of its secondary structure. Radius of gyration has been found to rise significantly with addition of surfactants and to fall down for high surfactants concentration. Similarly, a remarkable fall of secondary structure (α-helix content) has been observed, followed by its partial retrieval for high surfactants concentration. A strong aggregation of BSA has been observed for a confined range of surfactants concentrations as well. In case of HEWL-gemini system, on the other hand, the protein-surfactant interaction was found to be weak. Molecular mechanisms explaining such behaviour of protein-surfactant systems have been proposed. The differences of properties of both studied surfactants have also been discussed

The determination of present and possible environmental risks in solid waste dumping site, Tunceli, Turkey

Leachate was a major cause of high risk classification. This landfill was set as one with highest possible risk classification due to high vulnerability of private water wells to contamination from leachate flows. The aim of this study is to determine the present and possible environmental risks of the leachate spreading from solid waste dumping site in Tunceli and offer solutions for those determined environmental risks. For this purpose, the characteristics of the leachate were monitored at two station points detected in the solid waste dumping site for 7 months. The characteristics of the leachate were found for pH between 7.9 and 8.7. Oxidation reduction potential (ORP) occurred between − 143 and − 48 mV while conductivity was between 2.8 and 2.6 mS. Total solid matter (TSM) and suspended solid matter (SSM) were between 1000 and 7000 mg/l, 0.2–22.5 mg/l, respectively, while total volatile solids (TVS) occurred between 300 and 1800 mg/l for the two stations.Alkalinity was approximately between 290 and 5210 mg/l, while biological oxygen demand ( BOD5) and chemical oxygen demand (COD) results were 15–606 mg/l and 60–1160 mg/l, respectively, for two stations in all sampling time. In both stations, orthophosphate, ammonium nitrogen, nitrate, sulfate, and chloride analyses stayed between 3.04 and 921.1 mg/l; 0.29–619.36 mg/l; 8.94–135.04 mg/l; 125.9–1360.9 mg/l and 99.9–1249.9 mg/l, respectively, in 6 months. As a result of the characterization studies obtained from the leachate, it was found that the amounts of water entering into the waste mass and the retention period of the water in the mass were very effective in the temporal character change of the leachate. According to the Discharge Standards for Solid Waste Assessment and Disposal Facilities and Discharge to Waste Water Infrastructure Facilities of waste management regulation, the results were found to be risky. Consequently, the site in question needs to be urgently rehabilitated when considering the environmental risks of the leachate spreading from the site