AI Article Synopsis
Article Abstract
Although the protein synthesis inhibitor cycloheximide (CHX) has been known for decades, its precise mechanism of action remains incompletely understood. The glutarimide portion of CHX is seen in a family of structurally related natural products including migrastatin, isomigrastatin and lactimidomycin (LTM). We found that LTM, isomigrastatin and analogs have a potent antiproliferative effect on tumor cell lines and selectively inhibit translation. A systematic comparative study of the effects of CHX and LTM on protein synthesis revealed both similarities and differences between the two inhibitors. Both LTM and CHX were found to block the translocation step in elongation. Footprinting experiments revealed protection of a single cytidine nucleotide (C3993) in the E-site of the 60S ribosomal subunit, thus defining a common binding pocket for the two inhibitors in the ribosome. These results shed new light on the molecular mechanism of inhibition of translation elongation by both CHX and LTM.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831214 | PMC |
| http://dx.doi.org/10.1038/nchembio.304 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Motility-induced collapse of an active Brownian particle polymer chain.
Phys Chem Chem Phys
December 2024
Semenov Federal Research Center for Chemical Physics, Kosygina, 4, 119991 Moscow, Russia.
The ability of particles to transform absorbed energy into translational movements brings peculiar order into nonequilibrium matter. Connected together into a chain, these particles collectively behave completely differently from well-known equilibrium polymers. Examples of such systems vary from nanoscale to macroscopic objects.
View Article and Find Full Text PDFKnown from trees and the tropics: new insights into the species complex.
Stud Mycol
December 2024
Westerdijk Fungal Biodiversity Institute, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.
The species complex (FLSC) currently comprises 11 phylogenetic species, including accepted names such as , , and , which have mostly been reported in association with citrus and coffee. Many varieties were documented by Wollenweber & Reinking (1935), which is indicative of a wider diversity of species within this group. The lack of type material in some cases, especially for the older names, means that definition by molecular phylogeny is very difficult.
View Article and Find Full Text PDFProposal of one new family, seven new genera and seventy new basidiomycetous yeast species mostly isolated from Tibet and Yunnan provinces, China.
Stud Mycol
December 2024
School of Life Sciences, Institute of Life Sciences and Green Development, Hebei University, Baoding 071002, Hebei, China.
More than 2 000 yeast strains isolated from 1 200 samples mostly collected from Tibet and Yunnan provinces in China were identified as 462 species according to the internal transcribed spacer including the 5.8S rDNA (ITS) and the D1/D2 domains of the large subunit rDNA (LSU) sequence analyses. Among them, 70 new basidiomycetous yeast species were proposed based on the multi-locus phylogenetic analyses including the D1/D2 domains, the ITS, the small subunit rDNA (SSU), the largest subunit of RNA polymerase II (), the second largest subunit of RNA polymerase II () and translation elongation factor 1-α (), as well as the phenotypic comparisons.
View Article and Find Full Text PDFAchieving Photocatalytic Overall Nitrogen Fixation via an Enzymatic Pathway on a Distorted CoP4 Configuration.
Angew Chem Int Ed Engl
December 2024
Chinese Academy of Sciences Dalian Institute of Chemical Physics, State Key Laboratory of Catalysis, CHINA.
Photocatalytic nitrogen (N2) fixation over semiconductors has always suffered from poor conversion efficiency owing to weak N2 adsorption and the difficulty of N≡N triple bond dissociation. Herein, a Co single-atom catalyst (SAC) model with a C-defect-evoked CoP4 distorted configuration was fabricated using a selective phosphidation strategy, wherein P-doping and C defects co-regulate the local electronic structure of Co sites. Comprehensive experiments and theoretical calculations revealed that the distorted CoP4 configuration caused a strong charge redistribution between the Co atoms and adjacent C atoms, minimizing their electronegativity difference.
View Article and Find Full Text PDFIdentification of an antibiotic from an HTS targeting EF-Tu:tRNA interaction: a prospective topical treatment for MRSA skin infections.
Appl Environ Microbiol
December 2024
Department of Microbiology, Biochemistry, & Molecular Genetics, Rutgers New Jersey Medical School, Newark, New Jersey, USA.
Because of the urgent need for new antibiotics to treat drug-resistant bacterial pathogens, we employed an assay that rapidly screens large quantities of compounds for their ability to interfere with bacterial protein synthesis, in particular, the delivery of amino acids to the ribosome via tRNA and elongation factor Tu (EF-Tu). We have identified a drug lead, named MGC-10, which kills Gram-positive bacteria, including methicillin-resistant (MRSA), with a MIC of 6 µM, while being harmless to mammalian cells in that concentration range. The antibacterial activity of MGC-10 was broad against over 50 strains of antibiotic-resistant samples obtained from hospital infections, where MGC-10 inhibited all tested strains of MRSA.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!