Berberine potently inhibits protein tyrosine phosphatase 1B: investigation by docking simulation and experimental validation.
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.
Bustanji
Yasser
Y
Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, University of Jordan, Amman, Jordan. bustanji@ju.edu.jo
Taha
Mutasem O
MO
Yousef
Al-Motassem
AM
Al-Bakri
Amal G
AG
D001599:Berberine / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D003198:Computer Simulation; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008958:Models, Molecular; D011487:Protein Conformation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D015203:Reproducibility of Results; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D007004:Hypoglycemic Agents; D011994:Recombinant Proteins; D001599:Berberine; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases