Unknown

Dataset Information

0

Potent Human ?-Amylase Inhibition by the ?-Defensin-like Protein Helianthamide.


ABSTRACT: Selective inhibitors of human pancreatic ?-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 ?-amylase revealed that helianthamide adopts a ?-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 ?-defensin fold, which is rarely seen outside of its traditional role in antimicrobial peptides.

PROVIDER: S-EPMC4819454 | BioStudies |

REPOSITORIES: biostudies

Similar Datasets

| S-EPMC6835510 | BioStudies
1999-01-01 | S-EPMC1220419 | BioStudies
2000-01-01 | S-EPMC1221109 | BioStudies
| S-EPMC4848636 | BioStudies
| S-EPMC5793123 | BioStudies
| S-EPMC6971160 | BioStudies
| S-EPMC3397671 | BioStudies
| S-EPMC3119845 | BioStudies
| S-EPMC4447985 | BioStudies
| S-EPMC5920107 | BioStudies