title: 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.
authors.affiliation: Biophysical Chemistry Laboratory, Chemistry Division, CSIR-Indian Institute of Chemical Biology, 4, Raja SC Mullick Road, Kolkata 700 032, India. gskumar@iicb.res.in gskumar@csiriicb.in.
authors.forename: Chandrima
authors.initials: C
authors.lastname: Jash
authors.forename: Pritha
authors.initials: P
authors.lastname: Basu
authors.forename: Pavan V
authors.initials: PV
authors.lastname: Payghan
authors.forename: Nanda
authors.initials: N
authors.lastname: Ghoshal
authors.forename: Gopinatha Suresh
authors.initials: GS
authors.lastname: Kumar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D053119:Benzophenanthridines / Q000737:chemistry*; D001665:Binding Sites; D002151:Calorimetry; D002942:Circular Dichroism; D007546:Isoquinolines / Q000737:chemistry; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009113:Muramidase / Q000737:chemistry*; D011485:Protein Binding; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics
chemical_list: D000970:Antineoplastic Agents; D053119:Benzophenanthridines; D007546:Isoquinolines; C005705:sanguinarine; C016299:chelerythrine; C421864:hen egg lysozyme; D009113:Muramidase