The shape of motifs is important for RNA functions and deeply reflects the structure of RNA at the supersecondary level, an intermediate level between secondary and spatial structure. However, there is currently no standardized classification system for the RNA supersecondary structures. Primary and secondary occupied conformations, accounting for 73% of the nucleic acid backbone units, were found by extending the concept of protein supersecondary structure code (SSSC) combined with the conformational code for organic molecules.
View Article and Find Full Text PDFCharacterization and understanding of protein higher order structure (HOS) is essential at all stages of biologics development. Here, two folding variants of a bispecific monoclonal antibody, the correctly folded form and an alternative configuration with reduced potency, were characterized by several HOS characterization techniques. Specifically, differential scanning calorimetry (DSC), circular dichroism (CD), Fourier-transform infrared spectroscopy (FTIR), Raman and Raman optical activity (ROA) spectroscopy were used together to elucidate the impacts of disulfide bond scrambling in the fused scFv domains on the structure and thermal stability of the antibody.
View Article and Find Full Text PDFinfection has been recognized as an urgent threat to antifungal drug resistance, and the Eagle effect of FKS1 (1,3-β-d-glucan synthase) wild-type isolates has also been noted. The Eagle effect, namely, where higher concentrations of antifungals reduce fungicidal activity relative to lower concentrations, is a confounding factor of apparent antifungal resistance, but the detailed mechanism remains unclear. Here, we present the conformational variability of mutation sites for ERG11p (lanosterol 14α-demethylase) and FKS1 from deep neural network-based prediction along with the reported X-ray crystallographic and cryo-electron microscopy (cryo-EM) structures of antifungals.
View Article and Find Full Text PDFThe Omicron BA.1 variant of SARS-CoV-2 preferentially infects through the cathepsin-mediated endocytic pathway, but the mechanism of cell entry has not been solved yet because BA.4/5 is more fusogenic and more efficiently spread in human lung cells than BA.
View Article and Find Full Text PDFIdentifying the fundamental cause of transmissibility of multiple mutation strains and vaccine nullification is difficult in general and is a source of significant concern. The conformational variability of the mutation sites for B.1.
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