Identification of selective plant-derived natural carotenoid and flavonoids as the potential inhibitors of DHHC-mediated protein S-palmitoylation: an in silico study.
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.
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