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A novel ADP-directed chaperone function facilitates the ATP-driven motor activity of SARS-CoV helicase.
Nucleic Acids Res
January 2025
Single-Molecule and Cell Mechanobiology Laboratory, Daejeon, 34141, South Korea.
Helicase is a nucleic acid motor that catalyses the unwinding of double-stranded (ds) RNA and DNA via ATP hydrolysis. Helicases can act either as a nucleic acid motor that unwinds its ds substrates or as a chaperone that alters the stability of its substrates, but the two activities have not yet been reported to act simultaneously. Here, we used single-molecule techniques to unravel the synergistic coordination of helicase and chaperone activities, and found that the severe acute respiratory syndrome coronavirus helicase (nsp13) is capable of two modes of action: (i) binding of nsp13 in tandem with the fork junction of the substrate mechanically unwinds the substrate by an ATP-driven synchronous power stroke; and (ii) free nsp13, which is not bound to the substrate but complexed with ADP in solution, destabilizes the substrate through collisions between transient binding and unbinding events with unprecedented melting capability.
View Article and Find Full Text PDFDeployment and transcriptional evaluation of nitisinone, an FDA-approved drug, to control bed bugs.
Pest Manag Sci
January 2025
Department of Biological Sciences, University of Cincinnati, Cincinnati, OH, USA.
Background: Bed bugs are blood-feeders that rapidly proliferate into large indoor infestations. Their bites can cause allergies, secondary infections and psychological stress, among other problems. Although several tactics for their management have been used, bed bugs continue to spread worldwide wherever humans reside.
View Article and Find Full Text PDFGENI as an AMPK Activator Binds α and γ Subunits and Improves the Memory Dysfunction of Alzheimer's Disease Mouse Models via Autophagy and Neuroprotection.
Antioxidants (Basel)
January 2025
College of Pharmaceutical Sciences, Zhejiang University, Yu Hang Tang Road 866, Hangzhou 310058, China.
Geniposidic 4-isoamyl ester (GENI) with anti-aging effects is a new iridoid glycoside derivative from Ellis found in our previous study. In this study, to indicate whether this compound has anti-Alzheimer's disease (AD) effect, the galactose-induced AD mice and naturally aging mice with AD were used to do drug efficacy evaluation. Furthermore, the Western blot, small interfering RNA (siRNA), drug affinity responsive target stability (DARTS), cellular thermal shift assay (CESTA), liquid chromatography-tandem mass spectrometry (LC/MS-MS), adenosine 5'-monophosphate-activated protein kinase (AMPK) mutants and surface plasmon resonance (SPR) analysis were utilized to clarify the mechanism of action and identify target protein of this molecule.
View Article and Find Full Text PDFThe Role of Bitter-Tasting Substances in Salivation and Swallowing: Results of the Pilot Study.
Foods
January 2025
Federal Research Centre of Nutrition, Biotechnology and Food Safety, Moscow 109240, Russia.
The aim of this study was to investigate the effects of caffeine, vanillin, and epigallocatechin gallate on salivation and swallowing and to find ways to correct their negative effects. Solutions of these substances with an equivalent intensity of bitter taste were compared for this purpose. To compensate for their effect, solutions of adenosine monophosphate, saliva substitute, and their combination were used.
View Article and Find Full Text PDFDiscovery of the First Efficacious Adenosine 2A Receptor Negative Allosteric Modulators for High Adenosine Cancer Immunotherapies.
J Med Chem
January 2025
School of Pharmaceutical Sciences, University of Geneva, 1206 Geneva, Switzerland.
Inhibition of the adenosine 2A receptor (AR) is recognized as a promising immunotherapeutic strategy but is challenged by the ubiquity of AR function in the immune system. To develop a safe yet efficacious immunotherapy, the discovery of a novel negative allosteric modulator (NAM) was preferred. Leveraging an in-house, sensitive, high-throughput screening cellular assay, novel AR NAM scaffolds were identified, followed by an extensive structure-activity relationship (SAR) study, leading to the discovery of potent 2-amino-3,5-dicyanopyridine derivatives.
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