Chelerythrine–lysozyme interaction: spectroscopic studies, thermodynamics and molecular modeling exploration

Abstract

The binding of the iminium and alkanolamine forms of chelerythrine to lysozyme (Lyz) was investigated by spectroscopy and docking studies. The thermodynamics of the binding was studied by calorimetry. Spectroscopic evidence suggested that Trp-62 and Trp-63 in the β-domain of the protein are closer to the binding site; moreover, the binding site was at a distance of 2.27 and 2.00 nm from the iminium and alkanolamine forms, respectively, according to the Forster theory of non-radiation energy transfer. The equilibrium binding constants for the iminium and alkanolamine forms at 298 K were evaluated to be 1.29 × 10(5) and 7.79 × 10(5) M(-1), respectively. The binding resulted in an alteration of the secondary structure of the protein with a distinct reduction of the helical organization. The binding of iminium was endothermic, involving electrostatic and hydrophobic interactions, while that of alkanolamine form was exothermic and dominated by hydrogen bonding interactions. Docking studies provided the atomistic details pertaining to the binding of both forms of chelerythrine and supported the higher binding in favour of the alkanolamine over the iminium. Furthermore, molecular dynamics study provided accurate insights regarding the binding of both chelerythrine forms in accordance with the experimental results obtained. Chelerythrine binding pocket involves the catalytic region and aggregation prone K-peptide region, which are sandwiched between one another. Overall, these results suggest that both the forms of the alkaloid bind to the protein but the neutral form has higher affinity than the cationic form.

Elucidation of Binding Mechanism of Photodynamic Therapeutic Agent Toluidine Blue O with Chicken Egg White Lysozyme by Spectroscopic and Molecular Dynamics Studies

“…(B) that the CD signal of lysozyme showed a considerable perturbation upon the addition of TBO. This clearly points toward the possibility of slight alterations in the tertiary structure and/or enhanced flexibility of lysozyme . Moreover, the observed spectral alterations in both near‐ and far‐UV CD regions make it clear that the binding of TBO with lysozyme results in the structural changes in lysozyme conformation.…”

“…It is evident from Fig. (B) that major force of interaction involved in the binding of lysozyme with TBO is hydrophobic and hydrogen bond interaction . The calculated Gibbs energy change (Δ G ) value using the docking results for lysozyme–TBO system is −22.13 kJ mol −1 .…”

“…Upon the addition of TBO dye to ANS–lysozyme system, the emission intensity of ANS–lysozyme diminished by 25%. This notable reduction in emission intensity of ANS–lysozyme system suggests that TBO can fairly compete against ANS for binding sites .…”

Deciphering the Interaction of 5,7‐Dihydroxyflavone with Hen‐Egg‐White Lysozyme through Multispectroscopic and Molecular Dynamics Simulation Approaches

“…Recently our group has reported the interactions of 7‐hydroxyflavone, 3‐hydroxyflavone, naringenin and naringin with HEWL ,. In recent times, the interaction studies of several small ligands with HEWL have been reported . The multifarious pharmaceutical applications of dietary polyphenols due to their high bioactivity and low toxicity have accumulated tremendous interest among different research groups throughout the world.…”

“…[5,6] In recent times, the interaction studies of several small ligands with HEWL have been reported. [7][8][9][10] The multifarious pharmaceutical applications of dietary polyphenols due to their high bioactivity and low toxicity have accumulated tremendous interest among different research groups throughout the world. Flavonoids, a class of natural bioactive polyphenolic compounds found in various plants and fruits, are well recognized for their broad range of pharmaceutical and biological properties such as anti-oxidative, [11] anti-inflammatory, [12] anti-cancer, [13] anti-tumor, [14] etc and are also known to reduce the risk of diseases like cancer and stroke.…”