Endocrine disruption: In silico interactions between phthalate plasticizers and corticosteroid binding globulin

Area of Science:

• Endocrinology
• Environmental Health
• Toxicology

Background:

• Endocrine-disrupting compounds (EDCs) interfere with normal hormone function.
• Phthalate plasticizers are widely used industrial chemicals with known endocrine-disrupting properties.
• Corticosteroid-binding globulin (CBG) is crucial for cortisol transport and homeostasis.

Purpose of the Study:

• To investigate the potential of nine environmentally relevant phthalate plasticizers to disrupt CBG function.
• To analyze the binding interactions between phthalates and CBG at the molecular level.

Main Methods:

• Induced fit docking simulations were performed for nine phthalates against the CBG protein.
• Analysis of amino acid residue interactions and comparison with cortisol binding sites.

Main Results:

• Phthalates interacted with 10-19 amino acid residues in CBG, with significant overlap (53-82%) with cortisol binding sites.
• Five phthalates and cortisol shared a hydrogen bond with Arg-252.
• Long-chain phthalates showed higher binding affinity and more interactions with CBG than short-chain phthalates.

Conclusions:

• Phthalates exhibit structural similarities to cortisol in their binding to CBG.
• This suggests a potential for competitive binding, disrupting cortisol and progesterone homeostasis.
• Phthalates pose a risk to endocrine function through interference with CBG.