Potential toxicity of bisphenol A to α-chymotrypsin and the corresponding mechanisms of their binding

Bisphenol A (BPA) is an endocrine disruptor widely existing in plastics and resins, which can accumulate in animals and human bodies, posing a potential threat to the physiological and biochemical reactions of human beings or other organisms. alpha-Chymotrypsin is a kind of proteolytic enzyme existing in humans and animals, which can cause diseases when its activity is excessive. However, there is a lack of research on the mechanism of endocrine disruptors affecting alpha-chymotrypsin activity. In this study, the interaction between BPA and alpha-chymotrypsin was proved via multiple spectroscopic approaches, enzyme activity change, isothermal titration calorimetry and molecular docking. Results showed that alpha-chymotrypsin's polypeptide chains were unfolded, and protein skeletons were loosened with the exposure to BPA. alpha-Helix content increased and beta-sheet content was decreased. The particle size of the BPA-alpha-chymotrypsin complex became smaller. Fluorescence sensitization may also be explained by a perturbation of the chromophore Trp 141. The thermodynamic parameters of the binding reaction were measured by isothermal titration calorimetry (ITC), which showed that there was hydrophobic interaction between BPA and alpha-chymotrypsin, which was consistent with the results of molecular docking. Moreover, BPA may stop near the active center of alpha-chymotrypsin and interact with the key residues His 57 and Ser 195. The above phenomenon explained the result that the activity of alpha-chymotrypsin increased to 139% when exposed to high dose BPA (40 mu M). Taken together, the effects of BPA on the structure and function of alpha-chymotrypsin were clarified at the molecular level, which made up the gap in the mechanism of BPA on the proteolytic enzyme, and provided a reliable basis for disease avoidance and prevention.

Automated summary

This study investigated the mechanism of how Bisphenol A (BPA) affects the activity of alpha-chymotrypsin, a proteolytic enzyme. The results showed that BPA caused changes in the structure of alpha-chymotrypsin, leading to an increase in its activity. This study filled the research gap on the mechanism of BPA on proteolytic enzymes and provided a reliable basis for disease prevention.