One life, two strategies: Crucial structural differences between the human and the Plasmodium falciparum proteasomes were recently identified. A combination of cryo-EM and functional characterization enabled the design of a selective antimalarial proteasome inhibitor that shows low toxicity in the host. When used with artemisinin, this ligand offers a new approach for the efficient treatment of malaria at all stages of the parasite lifecycle.
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http://dx.doi.org/10.1002/anie.201602519 | DOI Listing |
Nucleic Acids Res
January 2025
Department of Chemistry and State Key Laboratory of Marine Pollution, City University of Hong Kong, Hong Kong SAR 999077, China.
RNA G-quadruplexes (rG4s) are non-canonical secondary nucleic acid structures found in the transcriptome. They play crucial roles in gene regulation by interacting with G4-binding proteins (G4BPs) in cells. rG4-G4BP complexes have been associated with human diseases, making them important targets for drug development.
View Article and Find Full Text PDFJ Med Chem
January 2025
Center for Molecular Oncology, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, 610064 Chengdu, China.
Cellular-mesenchymal epithelial transition factor (c-Met) is an attractive target for treating multiple cancers. Despite plentiful c-Met inhibitors have been developed, some issues, including the acquired drug resistance to c-Met inhibitors, have emerged to hamper their application in clinical treatment. Degradation of c-Met offers an opportunity to solve these issues.
View Article and Find Full Text PDFIUCrJ
March 2025
Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, 02-093 Warsaw, Poland.
Quantum crystallography methods have been employed to investigate complex formation between nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX) enzymes, with particular focus on the COX-1 and COX-2 isoforms. This study analyzed the electrostatic interaction energies of selected NSAIDs (flurbiprofen, ibuprofen, meloxicam and celecoxib) with the active sites of COX-1 and COX-2, revealing significant differences in binding profiles. Flurbiprofen exhibited the strongest interactions with both COX-1 and COX-2, indicating its potent binding affinity.
View Article and Find Full Text PDFBiochemistry
January 2025
Department of Biosciences and Bioengineering, Indian Institute of Technology, Roorkee, Uttarakhand 247667, India.
SARS-CoV-2 variant recurrence has emphasized the imperative prerequisite for effective antivirals. The main protease (Mpro) of SARS-CoV-2 is crucial for viral replication, making it one of the prime and promising antiviral targets. Mpro features several druggable sites, including active sites and allosteric sites near the dimerization interface, that regulate its catalytic activity.
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