Rifampicin Induced Aggregation of Ovalbumin: Malicious Behaviour of Antibiotics

Title:Rifampicin Induced Aggregation of Ovalbumin: Malicious Behaviour of Antibiotics

Volume: 22 Issue: 7

Author(s): Naveed A. Fazili, Gufran A. Siddiqui, Sheraz A. Bhat, Mohammad Afsar, Mohammad Furkan and Aabgeena Naeem

Affiliation:

Keywords: Aggregation, congo red, globular, intermediates, morphology, ovalbumin.

Abstract: Molecular modeling deciphered the site of interaction of rifampicin in the structure of ovalbumin at a site which is surrounded by residues Glu-214, Asp-98, Pro-85, Asp-91 and Asp-47. Isothermal calorimetric analysis determined the thermodynamic parameters i.e. ΔH and ΔS which came out be -8.086 cal/mol and -131 cal/mol/deg. respectively. Ovalbumin is a secretory protein of hen oviduct, present in the human blood serum and interacts with the drug rifampicin in vivo, when administered. Simulating these conditions in vitro revealed that rifampicin induced the aggregated state at 6 µM concentration which was featured by a decrease in the ANS fluorescence intensity relative to the native state while as the pre-molten and molten globule state were obtained at 3 µM and 5 µM concentration of rifampicin respectively displaying a hike in the ANS fluorescence intensity. Far-UV CD analysis suggested β-sheet rich structure with negative ellipticity peak at 217 nm for native ovalbumin incubated with 6 µM rifampicin. Increase in absorbance at 450 nm, red shift of 50 nm in the congo red binding assay and a hike of 10 fold in the ThT fluorescence intensity compared to the native state further confirmed aggregate formation. Moreover, TEM images displayed aggregates to be spherical morphologically. Aggregates formed at 6 µM rifampicin concentration were found to be cytotoxic as there was a reduction of cell viability to 28%. Thus, protein-drug interaction primarily facilitates a structural alteration in the native structure of proteins leading to their aggregation which were proved to be cytotoxic in nature.

Cite this article as:

Fazili A. Naveed, Siddiqui A. Gufran, Bhat A. Sheraz, Afsar Mohammad, Furkan Mohammad and Naeem Aabgeena, Rifampicin Induced Aggregation of Ovalbumin: Malicious Behaviour of Antibiotics, Protein & Peptide Letters 2015; 22 (7) . https://dx.doi.org/10.2174/0929866522666150526154240