Role of the conformational flexibility of evodiamine in its binding to protein hosts: a comparative spectroscopic and molecular modeling evaluation with rutaecarpine.

TitleRole of the conformational flexibility of evodiamine in its binding to protein hosts: a comparative spectroscopic and molecular modeling evaluation with rutaecarpine.
Publication TypeJournal Article
Year of Publication2014
AuthorsDomonkos, C, Fitos, I, Visy, J, Zsila, F
JournalPhys Chem Chem Phys
Volume16
Issue41
Pagination22632-42
Date Published2014 Nov 7
ISSN1463-9084
KeywordsBinding Sites, Circular Dichroism, Humans, Indole Alkaloids, Models, Molecular, Molecular Docking Simulation, Protein Binding, Protein Structure, Tertiary, Quinazolines, Serum Albumin, Spectrophotometry, Ultraviolet, Stereoisomerism
Abstract

Spectroscopic studies combined with computational analysis indicate the inherent conformational flexibility of the β-carbolin derivative evodiamine (EVD) featured with diverse pharmacological activities. Qualitative evaluation of the circular dichroism (CD) spectra of EVD enantiomers complemented with quantum chemical calculations reveals a chiral exciton signature that can be assigned to the folded, L-shaped conformation of the molecule. Changes of the exciton couplet measured in different solvents and the near-UV CD profile upon binding to human serum albumin (HSA) refer to the structural adaptability of EVD. The enantioselectivity of EVD-HSA interaction is demonstrated showing the binding preference of the (R)-enantiomer. Comparison of experimental and calculated CD spectra of various conformers of EVD as well as the results of molecular docking data suggest that the (R)-antipode is accomodated within the IIA subdomain of HSA in ridge-tile conformation. Rutaecarpine (RTC), the close congener of EVD, forms much tighter association complexes both with HSA and α1-acid glycoprotein. In contrast to EVD, the nearly planar geometry of the indoloquinazoline ring system of RTC allows its stacked dimeric binding to the HSA.

DOI10.1039/c4cp02483d
Alternate JournalPhys Chem Chem Phys
PubMed ID25231059