GPER binding site detection and description: A flavonoid-based docking and molecular dynamics simulations study.
J Steroid Biochem Mol Biol
; 239: 106474, 2024 05.
Article
in En
| MEDLINE
| ID: mdl-38307214
ABSTRACT
Flavonoids, a phenolic compounds class widely distributed in the plant kingdom, have attracted much interest for their implications on several health and disease processes. Usually, the consumption of this type of compounds is approximately 1 g/d, primarily obtained from cereals, chocolate, and dry legumes ensuring its beneficial role in maintaining the homeostasis of the human body. In this context, in cancer disease prominent data points to the role of flavonoids as adjuvant treatment aimed at the regression of the disease. GPER, an estrogen receptor on the cell surface, has been postulated as a probable orchestrator of the beneficial effects of several flavonoids through modulation/inhibition of various mechanisms that lead to cancer progression. Therefore, applying pocket and cavity protein detection and docking and molecular dynamics simulations (MD), we generate, from a cluster composed of 39 flavonoids, crucial insights into the potential role as GPER ligands, of Puerarin, Isoquercetin, Kaempferol 3-O-glucoside and Petunidin 3-O-glucoside, aglycones whose sugar moiety delimits a new described sugar-acceptor sub-cavity into the cavity binding site on the receptor, as well as of the probable activation mechanism of the receptor and the pivotal residues involved in it. Altogether, our results shed light on the potential use of the aforementioned flavonoids as GPER ligands and for further evaluations in in vitro and in vivo assays to elucidate their probable anti-cancer activity.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Molecular Dynamics Simulation
/
Neoplasms
Type of study:
Diagnostic_studies
Limits:
Humans
Language:
En
Journal:
J Steroid Biochem Mol Biol
Journal subject:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Year:
2024
Document type:
Article
Country of publication:
United kingdom