Inverted binding due to a minor structural change in berberine enhances its phospholipase A2 inhibitory effect
D Naveen Chandra1, Joseph Abhilash, G K Prasanth
1Department of Biotechnology & Microbiology and Inter University Centre for Bioscience, Kannur University, Palayad 670661, Kerala State, India.
International Journal of Biological Macromolecules
|February 7, 2012
Summary
Biotransformation of berberine using Rhizopus oryzae created hydroxyl derivatives with enhanced phospholipase A(2) inhibition. These compounds bind differently to PLA(2), showing potential as improved drug leads.
Area of Science:
- Microbial biotransformation
- Enzyme inhibition studies
- Structural biology
Background:
- Berberine is a natural compound with therapeutic potential.
- Phospholipase A(2) (PLA(2)) is a key target for drug development.
- Microbial biotransformation can modify natural products to enhance their activity.
Purpose of the Study:
- To investigate the biotransformation of berberine by Rhizopus oryzae.
- To evaluate the inhibitory potential of berberine derivatives against PLA(2).
- To elucidate the binding mode of biotransformed berberine to PLA(2).
Main Methods:
- Biotransformation using Rhizopus oryzae.
- Spectroscopic analyses: Fourier Transform Infrared (FTIR) spectroscopy, Nuclear Magnetic Resonance (NMR), Electro Spray Ionization-Mass Spectrometry (ESI-MS).
- Biochemical assays: Surface Plasmon Resonance (SPR) and enzyme kinetics.
- Structural determination: X-ray crystallography.
Main Results:
- Rhizopus oryzae demethylated berberine to hydroxyl derivatives.
- Biotransformed berberine derivatives exhibited higher inhibitory activity against PLA(2) compared to native berberine.
- X-ray crystal structures revealed an inverted binding orientation of biotransformed berberine to PLA(2).
Conclusions:
- Microbial biotransformation is a viable strategy for generating improved drug-lead compounds.
- Biotransformed berberine derivatives show enhanced efficacy and altered binding modes against PLA(2).
- This study highlights the potential of berberine derivatives in drug discovery.
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