Chromosomal loci jiggle in place between segregation events in prokaryotic cells and during interphase in eukaryotic nuclei. This motion seems random and is often attributed to brownian motion. However, we show here that locus dynamics in live bacteria and yeast are sensitive to metabolic activity. When ATP synthesis is inhibited, the apparent diffusion coefficient decreases, whereas the subdiffusive scaling exponent remains constant. Furthermore, the magnitude of locus motion increases more steeply with temperature in untreated cells than in ATP-depleted cells. This "superthermal" response suggests that untreated cells have an additional source of molecular agitation, beyond thermal motion, that increases sharply with temperature. Such ATP-dependent fluctuations are likely mechanical, because the heat dissipated from metabolic processes is insufficient to account for the difference in locus motion between untreated and ATP-depleted cells. Our data indicate that ATP-dependent enzymatic activity, in addition to thermal fluctuations, contributes to the molecular agitation driving random (sub)diffusive motion in the living cell.
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http://dx.doi.org/10.1073/pnas.1119505109 | DOI Listing |
J Mol Biol
February 2025
Department of Physics, University of Science and Technology of China, Hefei, Anhui 230026, China. Electronic address:
Protein phosphorylation is a fundamental cellular regulatory mechanism that governs the activation and deactivation of numerous proteins. In two-component signaling transduction pathways, the phosphorylation of response regulator proteins and their subsequent diffusion play pivotal roles in signal transmission. However, the impact of protein phosphorylation on their dispersion properties remains elusive.
View Article and Find Full Text PDFActa Trop
December 2024
Institute of Research and Development, Duy Tan University, Da Nang, Vietnam; School of Medicine and Pharmacy, Duy Tan University, Da Nang, Vietnam. Electronic address:
DNA gyrase, an ATP-dependent enzyme, plays a critical role in DNA replication, transcription, and recombination in Mycobacterium tuberculosis (MTB). While fluoroquinolones are effective antibacterial agents targeting DNA gyrase, their clinical use is often limited due to side effects and the emergence of bacterial resistance. In this study, we developed a quantitative structure-activity relationship (QSAR) model to predict the anti-tubercular activity of Quinoline-Aminopiperidine derivatives targeting the DNA gyrase enzyme, using a dataset of 48 compounds obtained from the literature.
View Article and Find Full Text PDFFront Mol Neurosci
October 2024
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, United States.
Sensorineural hearing loss (SNHL) is caused by damage to the mechanosensory hair cells and auditory neurons of the cochlea. The development of imaging tools that can directly visualize or provide functional information about a patient's cochlear cells is critical to identify the pathobiological defect and determine the cells' receptiveness to emerging SNHL treatments. However, the cochlea's small size, embedded location within dense bone, and sensitivity to perturbation have historically precluded high-resolution clinical imaging.
View Article and Find Full Text PDFCurr Med Chem
September 2024
Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.
Introduction: P-glycoprotein, an ATP-dependent efflux transporter, plays a crucial role in eliminating cellular toxins and affects the intracellular concentration and bioavailability of CDK 4/6 inhibitors. Moreover, dietary flavonoids are natural bio-enhancers that can effectively inhibit the efflux function of these transporters. Therefore, this study aimed to assess the impact of dietary polyphenols on the inhibition of P-glycoprotein and the subsequent efflux of CDK inhibitors palbociclib and ribociclib.
View Article and Find Full Text PDFNat Commun
July 2024
Department of Molecular Cell and Developmental Biology, University of California, Santa Cruz, CA, USA.
Fluctuations in the initiation rate of transcription, the first step in gene expression, ensue from the stochastic behavior of the molecular process that controls transcription. In steady state, the regulatory process is often assumed to operate reversibly, i.e.
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