Evaluation of the Binding Mechanism of Dietary Phytochemical, Ellagic Acid, with Human Transferrin: Spectroscopic, Calorimetric, and Computational Approaches Targeting Neurodegenerative Diseases.

Human transferrin (Htf) is vital in maintaining iron within the brain cells; any disruption results in the development of neurodegenerative diseases (NDs) and other related pathologies, especially Alzheimer's disease (AD). Ellagic acid (EA), a naturally occurring phenolic antioxidant, possesses neuroprotective potential and is present in a broad variety of fruits and vegetables. The current work explores the binding mechanism of dietary polyphenol, EA, with Htf by a combination of experimental and computational approaches. Molecular docking studies unveiled the binding of EA to Htf with good affinity. Molecular dynamic (MD) simulation further provided atomistic details of the binding process, demonstrating a stable Htf-EA complex formation without causing substantial alterations to the protein's conformation. Furthermore, fluorescence binding measurements indicated that EA forms a high-affinity interaction with Htf. Isothermal titration calorimetric measurements advocated the spontaneous nature of binding and also revealed the binding process to be exothermic. In conclusion, the study deciphered the binding mechanism of EA with Htf. The results demonstrated that EA binds with Htf with an excellent affinity spontaneously, thereby laying the groundwork for potential applications of EA in the realm of therapeutics for NDs in the context of iron homeostasis.