Potent Human α-Amylase Inhibition by the β-Defensin-like Protein Helianthamide
| Autor: | Adeleke Aguda, Leonard J. Foster, Jacqueline Wicki, Ethan D. Goddard-Borger, Gary D. Brayer, Christina Tysoe, Robert A. Keyzers, Stephen G. Withers, Leslie K. Williams, Nham T. Nguyen, Raymond J. Andersen, Suzanne Perry, Chris A. Tarling |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Barnase 030102 biochemistry & molecular biology Stichodactyla helianthus General Chemical Engineering Antimicrobial peptides Active site General Chemistry Biology medicine.disease_cause biology.organism_classification Fusion protein 3. Good health lcsh:Chemistry 03 medical and health sciences 030104 developmental biology lcsh:QD1-999 Biochemistry biology.protein medicine Glycoside hydrolase Amylase Escherichia coli Research Article |
| Zdroj: | ACS Central Science ACS Central Science, Vol 2, Iss 3, Pp 154-161 (2016) |
| ISSN: | 2374-7951 2374-7943 |
| Popis: | 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. Helianthamide represents the first of a novel class of glycosidase inhibitors and provides an unusual example of functional malleability of the β-defensin fold, which is rarely seen outside of its traditional role in antimicrobial peptides. We describe the discovery and structural characterization of helianthamide, a peptide with highly potent and selective inhibitory activity against human pancreatic α-amylase. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|