Comparative Molecular Characterization to Reveal Surface Behaviour of Non-proteolytic Bromelain Mutants.

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.