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

Area of Science:

• Biochemistry
• Molecular Biology
• Pharmacology

Background:

• Lysozyme (Lyz) is a crucial enzyme in the innate immune system.
• Chelerythrine, an alkaloid, exhibits various biological activities.
• Understanding chelerythrine's interaction with lysozyme is important for its therapeutic potential.

Purpose of the Study:

• To investigate the binding mechanisms and thermodynamics of chelerythrine's iminium and alkanolamine forms with lysozyme.
• To elucidate the structural alterations in lysozyme upon chelerythrine binding.
• To compare the binding affinities and interaction modes of the two chelerythrine forms.

Main Methods:

• Spectroscopy (fluorescence)
• Isothermal Titration Calorimetry (ITC)
• Förster Resonance Energy Transfer (FRET)
• Molecular Docking
• Molecular Dynamics simulations

Main Results:

• Chelerythrine binds to lysozyme, with the alkanolamine form exhibiting higher affinity (7.79 × 10^5 M⁻¹) than the iminium form (1.29 × 10^5 M⁻¹).
• Binding induces structural changes in lysozyme, reducing helical content.
• The iminium form binds endothermically via electrostatic and hydrophobic interactions, while the alkanolamine form binds exothermically, primarily through hydrogen bonding.
• Docking and molecular dynamics studies support the experimental findings, detailing the binding pocket within the catalytic and K-peptide regions.

Conclusions:

• Both iminium and alkanolamine forms of chelerythrine bind to lysozyme.
• The neutral alkanolamine form demonstrates superior binding affinity compared to the cationic iminium form.
• Chelerythrine's interaction with lysozyme involves significant structural and thermodynamic changes, highlighting its potential as a modulator of enzyme activity.