Title:Comparative Molecular Characterization to Reveal Surface Behaviour of Non-proteolytic Bromelain Mutants
Volume: 19
Issue: 11
Author(s): Soundhara G. Rajan, Ankita Sharma, Pooja Kumari and Sagarika Biswas*
Affiliation:
- Department of Genomics and Molecular Medicine, Institute of Genomics & Integrative Biology, Delhi,India
Keywords:
Rheumatoid arthritis, stem bromelain, molecular simulation, hormone-like-behaviour, NSAIDS, catalytic pockets.
Abstract: Background: Rheumatoid Arthritis (RA) is a chronic autoimmune disease that results in the
systemic inflammation principally affecting the capsule covering the articulating ends of the synovial
joints. Pharmacological treatment involving analgesics and anti-inflammatory drugs including steroids
suppresses the symptoms and has no effect on disease progression. However, disease modifying anti
rheumatic drugs (DMARD) used for the treatment were still analysed for their long-term effects.
Methods: Bromelain has been widely used as phytotherapeutic drug owing to its anti-inflammatory,
analgesic, anti-tumor and fibrinolytic properties. Bromelain refers to the combination of thiol proteases
available in the extract of Ananas comosus. The fibrinolytic property confers to the reduced pannus
development and hence the prevention of disease progression.
Results: It had been inferred that the observed clinical significance may not be solely accounted for its
proteolytic property but also may be due to its hormone-like behaviour (i.e.) non-canonical interactions
to initiate the signal transduction pathway. The hormone-like behaviour has been studied in cell models,
suggesting that bromelain acts at system level. In the present study, molecular behaviour of the
wild-type and mutant proteins has been studied by simulating the predicted structure in an aqueous
system. The comparative study of the mutants revealed that the mutant with both C26A and H158F
mutations has the similar surface properties compared to the other mutants and can be used in studying
the non-enzymatic interactions.
Conclusion: Thus, this study may prove to be a tool in experimental studies to understand the
hormone-like behaviour and in the construction of oral immunogenic synthetic peptides for treating inflamed
conditions.
