Journal:JBSD:29

Han ethnicity-specific type 2 diabetic treatment from traditional Chinese medicine?

Kuan-Chung Chen, Su-Sen Chang, Fuu-Jen Tsai, Calvin Yu-Chian Chen ^[1]

Molecular Tour
Insulin-degrading enzyme (IDE) is a zinc-metalloendopeptidase found mostly in cytosol. Since overexpression of IDE increases the rate of extracellular insulin degradation, IDE is a potential target for controlling insulin degradation.

The binding site of IDE protein bound with insulin (IDE protein colored in cyan and insulin colored in darkmagenta) is shown by the crystal structure 2g54. Leissring et al. (2010)^[2] also indicated a series of residues (colored in orange) and zinc ion in the catalytic site of IDE protein which interacted with their IDE inhibitors.

Virtual screening of the IDE protein (PDB ID: 2jg4) was conducted using the binding site defined by the catalytic site of IDE protein. In silico results indicate that traditional Chinese medicine compounds dihydrocaffeic acid (colored in royalblue), isopraeroside IV (colored in blueviolet), and scopolin (colored in chocolate) had high binding affinity with IDE protein and formed hydrogen bonds with the key active residue, Glu111 (colored in magenta) and other residues in the IDE binding site (colored in green). As the top three TCM compounds had stable interactions with zinc cation and residues in the catalytic site of IDE, they may block binding of other substrates, such as insulin, to the catalytic site. This competitive binding may limit the degradation of insulin. The top TCM candidates, dihydrocaffeic acid, isopraeroside IV, and scopolin, may have potential to be lead compounds for controlling insulin degradation for type 2 diabetes mellitus.