Potent Human α-Amylase Inhibition by the β-Defensin-like Protein Helianthamide.
Christina Tysoe, Leslie K Williams, Robert Keyzers, Nham T Nguyen, Chris Tarling, Jacqueline Wicki, Ethan D Goddard-Borger, Adeleke H Aguda, Suzanne Perry, Leonard J Foster, Raymond J Andersen, Gary D Brayer, Stephen G Withers
ACS Cent Sci | Published : 2016
Selective inhibitors of human pancreatic α-amylase (HPA) are an effective means of controlling blood sugar levels in the management of diabetes. A high-throughput screen of marine natural product extracts led to the identification of a potent (Ki = 10 pM) peptidic HPA inhibitor, helianthamide, from the Caribbean sea anemone Stichodactyla helianthus. Active helianthamide was produced in Escherichia coli via secretion as a barnase fusion protein. X-ray crystallographic analysis of the complex of helianthamide with porcine pancreatic α-amylase revealed that helianthamide adopts a β-defensin fold and binds into and across the amylase active site, utilizing a contiguous YIYH inhibitory motif. Hel..View full abstract