Inverted binding due to a minor structural change in berberine enhances its phospholipase A2 inhibitory effect.
Biotransformation of berberine by Rhizopus oryzae leads to its demethylation, producing hydroxyl derivatives, as revealed by Fourier Transform Infra Red spectroscopy, Nuclear Magnetic Resonance and Electro Spray Ionization-Mass Spectrometric analyses. Surface Plasmon Resonance and enzyme kinetic studies showed that biotransformed derivatives of berberine had a higher inhibitory potential than berberine towards phospholipase A(2). X-ray crystal structures demonstrated that biotransformed berberine binds to PLA(2) in an entirely different, inverted orientation with respect to the binding of berberine. This study brings out the significance of biotransformation in generation of better drug-lead compounds.
Department of Biotechnology & Microbiology and Inter University Centre for Bioscience, Kannur University, Palayad 670661, Kerala State, India.
D Naveen
DN
Chandra
Joseph
J
Abhilash
G K
GK
Prasanth
A
A
Sabu
C
C
Sadasivan
M
M
Haridas
D000818:Animals; D001599:Berberine / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001711:Biotransformation; D018360:Crystallography, X-Ray; D007700:Kinetics; D008958:Models, Molecular; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D012233:Rhizopus / Q000201:enzymology; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship; D013552:Swine
D064801:Phospholipase A2 Inhibitors; D001599:Berberine; D054467:Phospholipases A2