Berberine potently inhibits protein tyrosine phosphatase 1B: Investigation by docking simulation and experimental validation

Abstract

Berberine was investigated as an inhibitor of human protein tyrosine phosphatase 1B (h-PTP 1B) in an attempt to explain its anti-hyperglycemic activitiy. The investigation included simulated docking experiments to fit berberine within the binding pocket of h-PTP 1B. Berberine was found to readily fit within the binding pocket of h-PTP 1B in a low energy orientation characterized with optimal electrostatic attractive interactions bridging the isoquinolinium positively charged nitrogen atom of berberine and the negatively charged acidic residue of ASP 48 of h-PTP 1B. Experimentally, berberine was found to potently competitively inhibit recombinant h-PTP 1B in vitro (Ki value = 91.3 nM). Our findings strongly suggest that h-PTP 1B inhibition is at least one of the reasons for the reported anti-hyperglycemic activities of berberine.

Keywords::

• Berberine
• tyrosine phosphatase
• h-PTP 1B
• diabetes
• docking simulations
• inhibition

Acknowledgements

This project was sponsored by the Deanship of Scientific Research at the University of Jordan (grant number 19/2003–2004). The authors wish to thank the Deanship of Scientific Research and Hamdi-Mango Center for Scientific Research at the University of Jordan for providing funds towards purchasing O2 and Octane2 Sgi workstations and CERIUS2® software package.