Interaction of bovine serum albumin with anionic surfactants

The effect of binding and conformational changes induced by anionic surfactants sodium dodecyl sulfate (SDS) and sodium octyl sulfate (SOS) on bovine serum albumin (BSA) have been studied using differential scanning calorimetry (DSC), circular dichroism (CD), fluorescence and UV spectroscopic methods. The denaturation temperature, van't Hoff enthalpy and calorimetric enthalpy of BSA in the presence of SDS and SOS and urea at pH 7 have been determined. The results indicate that SDS plays two opposite roles in the folding and stability of BSA. It acts as a structure stabiliser at a low molar concentration ratio of SDS/BSA and as a destabilizer at a higher concentration ratio as a result of binding of SDS to denatured BSA. The Brandts and Lin model has been used to simulate the results

Adsorption of unfolded Cu/Zn superoxide dismutase onto hydrophobic surfaces catalyzes its formation of amyloid fibrils

Intracellular aggregates of superoxide dismutase 1 (SOD1) are associated with amyotrophic lateral sclerosis. In vivo, aggregation occurs in a complex and dense molecular environment with chemically heterogeneous surfaces. To investigate how SOD1 fibril formation is affected by surfaces, we used an in vitro model system enabling us to vary the molecular features of both SOD1 and the surfaces, as well as the surface area. We compared fibril formation in hydrophilic and hydrophobic sample wells, as a function of denaturant concentration and extraneous hydrophobic surface area. In the presence of hydrophobic surfaces, SOD1 unfolding promotes fibril nucleation. By contrast, in the presence of hydrophilic surfaces, increasing denaturant concentration retards the onset of fibril formation. We conclude that the mechanism of fibril formation depends on the surrounding surfaces and that the nucleating species might correspond to different conformational states of SOD1 depending on the nature of these surfaces

Metal-organic frameworks-derived titanium dioxide-carbon nanocomposite for supercapacitor applications

The pyrolysis of metal-organic frameworks (MOFs) to derive porous nanocarbons and metal oxides has attracted scientific attention due to the advantageous properties of the final products (eg, high surface areas). In the present research, MIL-125 (MIL = Materials of Institute Lavoisier, a Ti-based MOF) has been subjected to a single-step pyrolysis treatment in argon atmosphere. The combination of uniformly linked titanium metal cluster and oxygen-enriched organic linker has acted as a template to yield a titanium dioxide (TiO2)-carbon nanocomposite. The TiO2 nanoparticles infused in carbon skeleton structure (TiO2/C) has been investigated as an electrode material for supercapacitor applications. TiO2/C electrodes have delivered an excellent electrochemical performance, for example, in terms of charging-discharging efficiency. Two equally weighed TiO2/C electrodes have been used to assemble a solid-state symmetrical supercapacitor (SC) device, containing a gel electrolyte (poly vinyl alcohol in 1 M H2SO4). The above device has delivered a high value of energy density (43.5 Wh/kg) and an excellent power output of 0.865 kW/kg. The symmetrical SC could retain almost 95% of its initial capacitance even after 2000 charging-discharging cycles. The electrochemical performance of the TiO2/C SC was better than most MOF-based SCs reported previously. Such performance is attributed to the synergistic combination of electrically conducting MOF-derived carbon and redox active TiO2 nanocrystals with a large specific surface area

Stimulation of Heat Shock Protein 90 Chaperone Function Through Binding of a Novobiocin Analog KU-32

Heat shock protein 90 (Hsp90) is a eukaryotic chaperone responsible for the folding and functional activation of numerous client proteins, many of which are oncoproteins. Thus, Hsp90 inhibition has been intensely pursued, resulting in the development of many potential Hsp90 inhibitors, not all of which are well-characterized. Hsp90 inhibitors not only abrogate its chaperone functions, but also could help us gain insight into the structure-function relationship of this chaperone. Here, using biochemical and cell-based assays along with isothermal titration calorimetry, we investigate KU-32, a derivative of the Hsp90 inhibitor novobiocin (NB), for its ability to modulate Hsp90 chaperone function. Although NB and KU-32 differ only slightly in structure, we found that upon binding, they induce completely opposite conformational changes in Hsp90. We observed that NB and KU-32 both bind to the C-terminal domain of Hsp90, but surprisingly, KU-32 stimulated the chaperone functions of Hsp90 via allosteric modulation of its N-terminal domain, responsible for the chaperone\u27s ATPase activity. and studies indicated that upon KU-32 binding, Hsp90 undergoes global structural changes leading to the formation of a partially closed intermediate that selectively binds ATP and increases ATPase activity. We also report that KU-32 promotes HeLa cell survival and enhances the refolding of an Hsp90 substrate inside the cell. This discovery explains the effectiveness of KU-32 analogs in the management of neuropathies and may facilitate the design of molecules that promote cell survival by enhancing Hsp90 chaperone function and reducing the load of misfolded proteins in cells

In-Silico Drug Repurposing for Targeting SARS-CoV-2 Mpro

COVID-19, caused by novel coronavirus or SARS-CoV-2, is a viral disease which has infected millions worldwide. Considering the urgent need of the drug for fighting against this infectious disease, we performed in-silico drug repurposing. The main protease (Mpro) is one of the best characterized drug targets among coronaviruses, therefore, this was screened for already known drugs, including chemical constituents of Ayurvedic drugs, using docking and MD simulation. The results suggest EGCG, withaferin A and artesunate may act as potential inhibitors of the main protease (Mpro).</p

Heat capacity of folding of proteins corrected for disulfide cross-links

The heat capacities (&#916;Cp,f) for the temperature-induced folding of proteins: barnase, lysozyme T4, papain, trypsin, ribonuclease T1, chymotrypsin, lysozyme and ribonuclease A have been calculated from the change in solvent accessible surface area between the native state and extended polypeptide chain. To visualize the effect of disulfide cross-links on molar heat capacity, loops of varying number of alanine residues and extended alanine chains with terminal cystein are modeled. The difference in &#916;Cp values between the extended state and the loop conformation of proteins is linearly related to the number of residues in the loop. Corrections to the heat capacity of folding (&#916;Cp,f) are applied for proteins with cross-links based on this observation. There is good correlation between corrected values of &#916;Cp,f and experimental values

Switch in the Aggregation Pathway of Bovine Serum Albumin Mediated by Electrostatic Interactions

A strong denaturant, guanidinium hydrochloride (GdnHCl), is shown to delay and alter the inherent aggregation pathway of bovine serum albumin (BSA) from a downhill polymerization to a nucleated polymerization. We hypothesize that such an alteration is closely connected to the conformational population of the protein, and ion-binding to such an ensemble. Hindered molecular collisions due to electrostatic repulsions in an ion-bound denatured ensemble increase the activation barrier for aggregation to such an extent that the growth, which was spontaneous in the absence of any cosolute, goes through an unfavorable nucleation phase. Our study shows that the behavior in GdnHCl is not unique to it, but occurs in a certain class of cosolutesthose which are charged and bind to BSA. Variation in pH of the medium, which gives rise to extra charges on the protein backbone, also showed such repulsive effects, further confirming the involvement of electrostatic interactions. We have further shown that the coexistence of both an appropriate population and an appropriate cosolute is necessary. An absence of either of these prevents a switch in the pathway

Residues of Alpha Helix H3 Determine Distinctive Features of Transforming Growth Factor β3

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