"No one believes modeling results except the one who performed the calculation; ...everyone believes the experimental results except the one who did the measurements." P. J. Roache - Computational Physicist.
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J Ethnopharmacol
February 2025
Key Laboratory of Chinese Medicine Analysis, School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun, 130117, China. Electronic address:
Ethnopharmacological Relevance: The Anemonoides Raddeana (Rege) Holubhe is commonly employed in clinical practice as a traditional Chinese medicine for the treatment of conditions such as rheumatism and limb numbness. Raddeanin A (RA), an active compound derived from this Traditional Chinese Medicine (TCM), demonstrates specific anticancer properties against many tumorigeneses. However, the molecular mechanism underlying its effects on hepatocellular carcinoma (HCC) remains unexplored.
View Article and Find Full Text PDFMethods Mol Biol
January 2023
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.
Cryo-electron microscopy (cryo-EM) has become the mainstream technique for studying macromolecular structures. Determining the structures of protein complexes is more accessible to structural biologists than ever before. Nevertheless, obtaining high-resolution structures of molecular motors like dynein is still an extremely challenging goal due to their troublesome behaviors in ice, their exceedingly flexible conformations, and their intricate architectures.
View Article and Find Full Text PDFACS Bio Med Chem Au
October 2022
Division of Medicinal Chemistry and Pharmacognosy, The Ohio State University, Columbus, Ohio 43210, United States.
Drugs such as paclitaxel (Taxol) that bind microtubules are widely used for the treatment of cancer. Measurements of the affinity and selectivity of these compounds for their targets are largely based on studies of purified proteins, and only a few quantitative methods for the analysis of interactions of small molecules with microtubules in living cells have been reported. We describe here a novel method for rapidly quantifying the affinities of compounds that bind polymerized tubulin in living HeLa cells.
View Article and Find Full Text PDFJ Struct Biol
December 2022
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, USA. Electronic address:
Revealing high-resolution structures of microtubule-associated proteins (MAPs) is critical for understanding their fundamental roles in various cellular activities, such as cell motility and intracellular cargo transport. Nevertheless, large flexible molecular motors that dynamically bind and release microtubule networks are challenging for cryo-electron microscopy (cryo-EM). Traditional structure determination of MAPs bound to microtubules needs alignment information from the reconstruction of microtubules, which cannot be readily applied to large MAPs without a fixed binding pattern.
View Article and Find Full Text PDFiScience
January 2022
Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6229 ER Maastricht, The Netherlands.
Antiplatelet drugs targeting G-protein-coupled receptors (GPCRs), used for the secondary prevention of arterial thrombosis, coincide with an increased bleeding risk. Targeting ITAM-linked receptors, such as the collagen receptor glycoprotein VI (GPVI), is expected to provide a better antithrombotic-hemostatic profile. Here, we developed and characterized an ultra-high-throughput (UHT) method based on intracellular [Ca] increases to differentiate GPVI and GPCR effects on platelets.
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