Solutions of monoclonal antibodies (mAbs) can show increased viscosity at high concentration, which can be a disadvantage during protein purification, filling, and administration. The viscosity is determined by protein-protein-interactions, which are influenced by the antibody's sequence as well as solution conditions, like pH, buffer type, or the presence of salts and other excipients. To predict viscosity, experimental parameters, like the diffusion interaction parameter (kD), or computational tools harnessing information derived from primary sequence, are often used, but a reliable predictive tool is still missing.
View Article and Find Full Text PDFIntroduction Hepatitis B virus (HBV) is the leading cause of cirrhosis in the developing world. Despite the development of effective vaccine(s) and direct-acting antivirals (DAAs) such as tenofovir and entecavir, the eradication of chronic HBV remains a distant dream in endemic regions. Factors such as treatment naivety, longer duration of disease, late diagnosis, family history of liver disorders and hepatocellular carcinoma, fatty liver disease, multiple comorbidities, alcoholism, use of tobacco products, noncompliance to drugs, and loss to follow-up all contribute to disease progression and development of complications.
View Article and Find Full Text PDFIntroduction Asthma is a clinical syndrome characterized by reversible and recurrent airway obstruction leading to the symptoms of wheezing, cough, shortness of breath, fatigue, and respiratory distress. It is one of the most common lung pathologies worldwide. Its incidence is on the rise in Pakistan, which may be due to overt environmental pollution or improving screening protocols.
View Article and Find Full Text PDFOur goal was to gain a better understanding of how protein stability can be increased by improving beta-turns. We studied 22 beta-turns in nine proteins with 66-370 residues by replacing other residues with proline and glycine and measuring the stability. These two residues are statistically preferred in some beta-turn positions.
View Article and Find Full Text PDFUsing cryo-electron microscopy, we have solved the structure of an icosidodecahedral COPII coat involved in cargo export from the endoplasmic reticulum (ER) coassembled from purified cargo adaptor Sec23-24 and Sec13-31 lattice-forming complexes. The coat structure shows a tetrameric assembly of the Sec23-24 adaptor layer that is well positioned beneath the vertices and edges of the Sec13-31 lattice. Fitting the known crystal structures of the COPII proteins into the density map reveals a flexible hinge region stemming from interactions between WD40 beta-propeller domains present in Sec13 and Sec31 at the vertices.
View Article and Find Full Text PDFStudies that compare proteins from thermophilic and mesophilic organisms can provide insights into ability of thermophiles to function at their high habitat temperatures and may provide clues that enable us to better define the forces that stabilize all proteins. Most of the comparative studies have focused on thermal stability and show, as expected, that thermophilic proteins have higher Tm values than their mesophilic counterparts. Although these comparisons are useful, more detailed thermodynamic analyses are required to reach a more complete understanding of the mechanisms thermophilic protein employ to remain folded over a wider range of temperatures.
View Article and Find Full Text PDFA thermodynamic stability study of five histidine-containing phosphocarrier protein (HPr) homologues derived from organisms inhabiting diverse environments is described. These HPr homologues are from Bacillus subtilis (Bs), Streptococcus thermophilus (St), Bacillus staerothermophilus (Bst), Bacillus halodurans (Bh), and Oceanobacillus iheyensis (Oi). Analyses of solvent and thermal denaturation experiments provide the cardinal thermodynamic parameters, like deltaG, deltaH, deltaS, T(m), and deltaC(p), that characterize the conformational stability for each homologue.
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