Abstract
Steady state and time resolved fluorescence spectroscopy, combined with molecular dynamics simulation, have been used to explore the interactions of a therapeutically important bioflavonoid, genistein, with normal human hemoglobin (HbA). Binding constants estimated from the fluorescence studies were K = (3.5 0.32) 10 4 M −1 for genistein. Specific interactions with HbA were confirmed from flavonoid-induced fluorescence quenching of the tryptophan in the protein HbA. The mechanism of this quenching involves both static and dynamic components as indicated by: (a) increase in the values of Stern-Volmer quenching constants with temperatures, (b) 0 / is slightly > 1 (where 0 and are the unquenched and quenched tryptophan fluorescence lifetimes (averaged) respectively). Molecular docking and dynamic simulations reveal that genistein binds between the subunits of HbA, ~18 A away from the closest heme group of chain α1, emphasizing the fact that the drug does not interfere with oxygen binding site of HbA.
Highlights
Flavonoids are polyphenolic compounds which are ubiquitous in plants of higher genera [1]
Molecular docking and dynamic simulations reveal that genistein binds between the subunits of HbA, ~18 Å away from the closest heme group of chain α1, emphasizing the fact that the drug does not interfere with oxygen binding site of HbA
AutoDock4 [19] was employed to gain an insight into the genistein binding with HbA. 3-D atomic coordinates of HbA were obtained from the Brookhaven Protein Data Bank (PDB ID 2D60) and prepared for docking
Summary
Flavonoids are polyphenolic compounds which are ubiquitous in plants of higher genera [1]. The isoflavone genistein (structure shown in Scheme 1) has dual action as a topoisomerase inhibitor and a tyrosine kinase inhibitor and induces cell differentiation [7,8]. Genistein, has been shown to be a specific inhibitor of the EGF stimulated tyrosine kinase activity in cultured A431 cells [7]. Consumption of the flavonoids has been associated with the prevention of several degenerative diseases [1,2,3,4,5,6], their bioavailability is often poor probably due to their low aqueous solubility and possible interaction with plasma proteins [11]. Hemoglobin is the most abundant blood protein and consists of two α and two β subunits which are noncovalently associated within erythrocytes as a 64.5 kDa tetramer [14,15]. Explored the interaction of genistein with human HbA using the intrinsic fluorescence of HbA and molecular dynamics approaches
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