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Identification of selective plant-derived natural carotenoid and flavonoids as the potential inhibitors of DHHC-mediated protein S-palmitoylation: an in silico study.
Chaturvedi, Suchi; Pandya, Nirali; Sadhukhan, Sushabhan; Sonawane, Avinash.
Afiliación
  • Chaturvedi S; Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, Madhya Pradesh, India.
  • Pandya N; Department of Chemistry, National University of Singapore, Singapore, Singapore.
  • Sadhukhan S; Department of Pharmacology and Regenerative Medicine, University of Illinois Chicago, Chicago, IL, USA.
  • Sonawane A; Department of Chemistry, Indian Institute of Technology Palakkad, Palakkad, Kerala, India.
J Biomol Struct Dyn ; : 1-14, 2024 Feb 06.
Article en En | MEDLINE | ID: mdl-38319030
ABSTRACT
Protein S-palmitoylation mediated by DHHCs is recognized as a distinct and reversible form of lipid modification connected with several health perturbations, including neurodegenerative disorders, cancer, and autoimmune conditions. However, the pharmacological characteristics of current pan-DHHC inhibitors, particularly their toxicity and off-target effects, have hindered their in-depth cellular investigations. The therapeutic properties of the natural compounds, with minimal side effects, allowed us to evaluate them as DHHC-targeting inhibitors. Here, we performed an insilico screening of 115 phytochemicals to assess their interactions with the DHHC20 binding site. Among these compounds, lutein, 5-hydroxyflavone, and 6-hydroxyflavone exhibited higher binding energy (-9.2, -8.5, and -8.5 kcal/mol) in the DHHC20 groove compared to pan-DHHC inhibitor 2-BP (-7.0 kcal/mol). Furthermore, we conducted a 100 ns MD simulation to evaluate the stability of these complexes under physiological conditions. The MDsimulation results indicated that DHHC20 formed a more stable conformation with lutein compared to 5-hydroxyflavone and 6-hyroxyflavone via hydrophobic and H-bond interactions. Conclusively, these results could serve as a promising starting point for exploring the use of these natural molecules as DHHC20 inhibitors.Communicated by Ramaswamy H. Sarma.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Diagnostic_studies / Prognostic_studies Idioma: En Revista: J Biomol Struct Dyn Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Diagnostic_studies / Prognostic_studies Idioma: En Revista: J Biomol Struct Dyn Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Reino Unido