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Structure of coxsackievirus cloverleaf RNA and 3C dimer establishes the RNA-binding mechanism of enterovirus protease 3C.
Sci Adv
March 2025
Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN 47405, USA.
In positive-strand RNA viruses, the genome serves as a template for both protein translation and negative-strand RNA synthesis. Enteroviruses use the cloverleaf RNA structure at the 5' end of the genome to balance these two processes. Cloverleaf acts as a promoter for RNA synthesis and forms a complex with viral 3CD protein, the precursor to 3C protease, and 3D polymerase.
View Article and Find Full Text PDFIs There Polyamorphism in Amorphous Indomethacin? Investigating the Physicochemical Properties of Amorphous Indomethacin with Different Thermal History.
Mol Pharm
March 2025
Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
Polyamorphism in organic molecules is a poorly understood and controversial phenomenon related to amorphous materials. Although very few studies, including our own, have demonstrated the existence of polyamorphism in drug molecules, this solid-state phenomenon is still very elusive and the investigation of its occurrence in other drugs is fundamental to understand its formation. Indomethacin (IND) has been recently discussed in the literature as a potential drug exhibiting polyamorphism.
View Article and Find Full Text PDFMechanistic Insights into Regioselectivity and Its Evolution in On-Surface Polymerization.
J Am Chem Soc
March 2025
CAS Key Laboratory of Molecular Nanostructure and Nanotechnology, CAS Research/Education Center for Excellence in Molecular Sciences, Beijing National Laboratory for Molecular Sciences (BNLMS), Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
Surface-catalyzed polymerization is crucial in both chemical science and industrial manufacturing, yet achieving regioselective radical polymerization on the surface remains challenging. Here, we demonstrate the regioselective Ullmann polymerization of nonsymmetrical 2,8-dibromoquinoline (DBQ) on an Au(111) surface. By combining scanning tunneling microscopy, density functional theory calculations, and kinetic modeling, we reveal the regioselectivity and its evolution with surface temperature at the molecular level.
View Article and Find Full Text PDFA family of bacterial actin homologs forms a three-stranded tubular structure.
Proc Natl Acad Sci U S A
March 2025
Department of Biochemistry, University of Washington, Seattle, WA 98195.
The cytoskeleton is crucial for cell organization and movement. In Eukaryotes, it largely consists of the protein actin, that forms a double-stranded linear filamentous structure in the presence of ATP and disassemble upon ATP hydrolysis. Bacteria also possess actin homologs, that drive fundamental cellular processes, including cell division, shape maintenance, and DNA segregation.
View Article and Find Full Text PDFProteasomal processing of the viral replicase ORF1 facilitates HEV-induced liver fibrosis.
Proc Natl Acad Sci U S A
March 2025
Department of Hepatobiliary and Pancreatic Surgery and Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
Chronic infections with hepatitis E virus (HEV), especially those of genotype 3 (G3), frequently lead to liver fibrosis and cirrhosis in patients. However, the causation and mechanism of liver fibrosis triggered by chronic HEV infection remain poorly understood. Here, we found that the viral multiple-domain replicase (ORF1) undergoes unique ubiquitin-proteasomal processing leading to formation of the EV-erived MAD ctivator (HDSA), a viral polypeptide lacking putative helicase and RNA polymerase domains.
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