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An Integrative Computational Approach for the Identification of C-Abl Kinase Inhibitors from Anti-Parkinson Plant-Derived Bioactive.
Med Chem
January 2025
Department of Chemistry and Biochemistry, Faculty of Medicine and Pharmacy, Ibn Zohr University, Laayoune 70000, Morocco.
Background: Oxidative stress is strongly linked to neurodegeneration through the activation of c-Abl kinase, which arrests α-synuclein proteolysis by interacting with parkin interacting substrate (PARIS) and aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2). This activation, triggered by ataxia-telangiectasia mutated (ATM) kinase, leads to dopaminergic neuron loss and α-synuclein aggregation, a critical pathophysiological aspect of Parkinson's disease (PD). To halt PD progression, pharmacological inhibition of c-Abl kinase is essential.
View Article and Find Full Text PDFPredicting the polyspecificity of aminoacyl-tRNA synthetase for non-canonical amino acids using molecular dynamics simulation and MM/PBSA.
PLoS One
January 2025
Department of Biotechnology and Bioengineering, Chonnam National University, Gwangju, Republic of Korea.
With the advancement of genetic code expansion, the field is progressing towards incorporating multiple non-canonical amino acids (ncAAs). The specificity of aminoacyl-tRNA synthetases (aaRSs) towards ncAAs is a critical factor, as engineered aaRSs frequently show polyspecificity, complicating the precise incorporation of multiple ncAAs. To address this challenge, predicting binding affinity can be beneficial.
View Article and Find Full Text PDFA non-canonical role for the tyrosyl tRNA synthetase: YARS regulates senescence induction and escape and controls the transcription of LIN9.
FEBS J
January 2025
Université d'Angers, Inserm, CNRS, CRCI2NA, ICO, Angers, France.
Senescence is a tumor suppressor mechanism triggered by oncogene expression and chemotherapy treatment. It orchestrates a definitive cessation of cell proliferation through the activation of the p53-p21 and p16-Rb pathways, coupled with the compaction of proliferative genes within heterochromatin regions. Some cancer cells have the ability to elude this proliferative arrest but the signaling pathways involved in circumventing senescence remain to be characterized.
View Article and Find Full Text PDFTranscriptome analysis reveals the potential mechanism of plateau environment on muscle growth and development in yak.
Comp Biochem Physiol Part D Genomics Proteomics
December 2024
Institute of Animal Husbandry and Veterinary, Tibet Autonomous Regional Academy of Agricultural Sciences, Lhasa, Tibet 850000, China. Electronic address:
Yak meat plays a significant economic role for yaks. The unique environment of the Qinghai-Tibet plateau profoundly impacts the meat production performance of yaks. Yet, the regulatory mechanisms influencing muscle growth and development in yaks within this plateau environment remain poorly understood.
View Article and Find Full Text PDFRendering Proteins Fluorescent Inconspicuously: Genetically Encoded 4-Cyanotryptophan Conserves Their Structure and Enables the Detection of Ligand Binding Sites.
Angew Chem Int Ed Engl
December 2024
ARC Centre of Excellence for Innovations in Peptide & Protein Science, Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.
Cyanotryptophans (CN-Trp) are privileged multimodal reporters on protein structure. They are similar in size to the canonical amino acid tryptophan and some of them exhibit bright fluorescence which responds sensitively to changes in the environment. We selected aminoacyl-tRNA synthetases specific for 4-, 5-, 6-, and 7-CN-Trp for high-yield in vivo production of proteins with a single, site-specifically introduced nitrile label.
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