Designing of enzyme inhibitors based on active site specificity: lessons from methyl gallate and its lipoxygenase inhibitory profile

Abstract

Methyl gallate was purified, by lipoxygenase (LOX) inhibitory activity-guided method since its alleged anti-inflammatory property, from Bergenia ligulata (Wall), a plant used in the traditional, Ayurvedic system of medicine extensively. The LOX inhibitory property of methyl gallate was studied by enzyme kinetics, isothermal titration calorimetry and molecular docking followed by molecular simulation studies. The wet-laboratory experiments and in silico studies showed complete agreement, and promise of methyl gallate as a drug-lead molecular scaffold for anti-inflammatory therapy, based on LOX inhibition. The expressed work shows the need of nonactive site binding parameters to be considered while designing of inhibitors based on the specificities toward active sites of enzymes.

Keywords:

• Methyl gallate
• lipoxygenase inhibition
• isothermal titration calorimetry
• molecular dynamics

Acknowledgments

The authors gratefully acknowledge the ‘Bioinformatics Infrastructure Facility’ (supported by DBT, Government of India) located at the Department of Biotechnology & Microbiology, Kannur University for providing the computational work. SCS thanks CSIR for Senior Research Fellowship. MH acknowledges the Kerala State Council for Science, Technology & Environment for the Emeritus Scientist position.

Disclosure statement

The authors indicate no potential conflicts of interest.

Additional information

Funding

This work was funded by the Council for Scientific and Industrial Research (India) [09/979(0007)/216-EMR-I (SRF)].