Structural and functional changes of catalase through interaction with Erlotinib hydrochloride. Use of Chou's 5-steps rule to study mechanisms

Abstract

Erlotinib hydrochloride (Erlo) is used in the treatment of non-small cell lung cancer, pancreatic cancer and other types of cancer. Interaction of small molecules with bio-macromolecules can lead to changes in the structure and function of them which is one of the possible side effects of the drugs. In this study, the interaction of Erlo with bovine liver catalase (BLC) using spectroscopic and computational methods is presented in detail. The enzymatic function of BLC decreased to 58.7% when the concentration of the Erlo was 0.5 × 10−7 M. Fluorescence results revealed that the combination of BLC with Erlo undergoes static quenching mechanism (Kb = 1.15 × 104 M−1 at 300 K). The interaction process was spontaneous, exothermic and enthalpy-driven and Van der Waals and hydrogen bonds forces played major roles in the this process. UV–Vis, CD, 3D, and synchronous fluorescence measurements indicated the changes in the microenvironment residues and α-helix contents of BLC in the presence of Erlo. Docking and molecular dynamics presented a stable binding configuration and their results were perfectly consistent with the spectroscopic results. Theoretical calculations and experimental analysis help to fully understand of drug interaction with important biological molecules such as enzymes.