Structural Chemistry of Helicase Inhibition

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

Helicases are essential motor enzymes that couple nucleoside-triphosphate hydrolysis with DNA or RNA strand unwinding. integral to replication, transcription, splicing, and translation of the genome, play crucial roles in proliferation cancer cells propagation viral pathogens, implicated neurodegenerative diseases. Despite their therapeutic potential, drug discovery efforts targeting helicases face significant challenges due dynamic enzymatic cycles, transient nature conformational states, conservation active sites. Analysis cocrystal structures inhibitor–helicase complexes revealed four distinct mechanisms inhibition: allosteric, ATP-competitive, RNA-competitive, interfacial inhibitors. While these static X-ray reveal potential binding pockets may support development selective drugs, application advanced techniques such as cryo-EM, single-molecule analysis, computational modeling will be for understanding helicase dynamics designing effective

Language: Английский

Structural Exploration of the PfBLM Helicase-ATP Binding Domain and Its Implications in the Quest for Antimalarial Therapies

Journal of Vector Borne Diseases, Journal Year: 2024, Volume and Issue: 61(3), P. 389 - 399

Published: Jan. 30, 2024

Background & objectives: The battle against malaria has witnessed remarkable progress in recent years, characterized by increased funding, development of life-saving tools, and a significant reduction disease prevalence. Yet, the formidable challenge drug resistance persists, threatening to undo these gains. Methods: To tackle this issue, it is imperative identify new effective candidates parasite that exhibit minimal toxicity. This study focuses on discovering such targeting PfRecQ1, also known as PfBLM, vital protein within Plasmodium falciparum . PfRecQ1 plays crucial role parasite’s life cycle DNA repair processes, making an attractive target. employs advanced computational techniques, including molecular modeling, structure-based virtual screening (SBVS), ADMET profiling, docking, dynamic simulations. Results: sources ligand molecules from extensive MCULE database utilizes strict filters ensure compounds meet essential criteria. Through research identifies MCULE-3763806507-0-9 promising antimalarial candidate, surpassing binding affinity potential drugs. However, underscore drug-like properties are primarily based silico experiments, wet lab experiments necessary validate candidates’ therapeutic potential. Interpretation conclusion: represents critical step addressing fight malaria.

Language: Английский

Characterization and organization of telomeric-linked helicase (tlh) gene families in Fusarium oxysporum

Current Genetics, Journal Year: 2024, Volume and Issue: 70(1)

Published: Nov. 12, 2024

Language: Английский