Molecular interaction of benzo-a-pyrene inhibits the catalytic activity of catalase: Insights from biophysical and computational studies

Abstract

Benzo-a-pyrene (BaP) is a polycyclic aromatic hydrocarbon, which alters the redox balance and results into oxidative stress. Among antioxidant enzymes, catalase plays a vital role in neutralizing the harmful effects of pollutant-induced oxidative stress. However, the molecular mechanism underlying the interaction of catalase with BaP is poorly understood. In this communication, structural and functional alterations of bovine liver catalase (BLC) in presence of BaP have been investigated at molecular and cellular levels. Reduced catalase activity is evident after BaP treatment in mouse embryonic fibroblast cell lines. Nevertheless, the enzyme activity of BLC in response to BaP was gradually decreased in Phosphate, HEPES, MOPS, and Tris buffers. The secondary conformation of BLC has altered considerably (decrease in α-helix and increase in other secondary structures) due to BaP exposure. In addition, molecular interaction study shows BaP binds near proximity to the active site of BLC with binding affinity of -11.2 kcal/mol. Molecular simulation determined the structural modifications in the protein, which indicate maximum fluctuations of BLC occured between 20-60, 160-180 and 380-440 amino acid residues. Amino acids like Leu175, Ala249, Ala250 and Ala253 are observed to interact with BaP over 100 ns trajectory through hydrophobic interaction. In summary, this integrated study comprising experimental, in vitro and in silico approaches presents a mechanistic insights towards BaP driven compromised conformation and catalytic activity of catalase.