Determination of Structural Factors Contributing to Protection of Zinc Fingers in Estrogen Receptor α through Molecular Dynamic Simulations.

ABSTRACT: The ERα transcription factor that induces tumor growth is a potential target for breast cancer treatment. Each monomer of the ERα DNA-binding domain (ERαDBD) homodimer has two conserved (Cys)₄-type zinc fingers, ZF1 (N-terminal) and ZF2 (C-terminal). Electrophilic agents release Zn²⁺ by oxidizing the coordinating Cys of the more labile ZF2 to inhibit dimerization and DNA binding. Microsecond-length molecular dynamics (MD) simulations show that greater flexibility of ZF2 in the ERαDBD monomer leaves its Cys more solvent accessible and less shielded from electrophilic attack by sulfur-centered hydrogen bonds than ZF1 which is buried in the protein. In the unreactive DNA-bound dimer, the formation of the dimer interface between the highly flexible D-box motif of ZF2 decr

SUBMITTER: Lutz PB 

PROVIDER: S-EPMC11873919 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature