Potential Binding Sites for Taurine on the Insulin Receptor: A Molecular Docking Study.

Abstract

Taurine has been reported to improve the action of insulin in normal, pre-, and diabetic conditions. However, the mechanism by which this amino acid ameliorates insulin sensitivity is not yet completely understood. Insulin acts on target tissues by interacting with the extracellular portion of a tyrosine kinase receptor, whose structure is known as the ectodomain (ECD) of the insulin receptor (IR). Some studies indicate that taurine can bind to the IR, which would contribute to its beneficial actions on glucose homeostasis. However, the binding mode of the amino acid on the IR ECD is unknown. Herein, using in silico experiments, we aimed to verify whether taurine may be an agonist of the IR and also to demonstrate the potential binding sites of taurine on the IR ECD. Molecular modeling predicted that taurine might interact with the three largest pocket sites for ligands present in the IR ECD. Taurine demonstrated high-energy interactions with these pockets, showing the highest affinity and highest molecular interaction with pocket 1, followed by decreasing energies and binding to pockets 2 and 3 of the IR ECD. The taurine interaction sites on the IR were not the same as the insulin interaction sites. Thus, these data indicate that taurine may be an agonist of the IR ECD, acting with high affinity at pocket 1 of the ECD. The predicted binding sites observed in this study probably constitute the regions of interaction of taurine on the IR and contribute to the mechanism by which taurine ameliorates insulin signaling pathway activation, thereby improving glucose homeostasis and the other cellular functions that are regulated by this intracellular signaling cascade.