Probing the interaction of fisetin with human serum transferrin via spectroscopic and molecular docking approaches.

The binding of fisetin to human serum transferrin (HST) was investigated by spectroscopic (steady-state fluorescence, synchronous fluorescence, Förster resonance energy transfer) and molecular docking approaches. HST fluorescence is quenched by fisetin by a static process. The binding takes place with a moderate affinity and it is driven by hydrogen bonding and van der Waals forces. Synchronous fluorescence study indicates that Trp is more involved in the fluorescent quenching of HST by fisetin than Tyr. The energy transfer between HST and fisetin occurs at a distance of 2.31 nm confirming the results obtained by fluorescence. The binding of fisetin to HST favors thermal denaturation of HST conformation. The transition temperature for HST was obtained at 53.81 °C while the presence of the fisetin led to its change to 49.06 °C. The molecular docking of fisetin to HST confirms the results obtained by the spectroscopic experiments showing a moderate affinity of fisetin for HST.Communicated by Ramaswamy H. Sarma.

Structural and molecular aspects of flavonoids as ligands for serum transferrin.

Human serum transferrin (HST) acts as a carrier for Fe3+ and other ions. Binding of flavonoids to HST produces changes in the protein structure with direct implication on iron delivery into cells. We investigate the binding mechanism and affinity towards HST of three flavonoids: rutin, luteolin, and apigenin by different techniques: UV-Vis, fluorescence, fluorescence resonance energy transfer (FRET) combined with molecular docking. UV-Vis results indicate an interaction between flavonoids and HST. It was observed that HST fluorescence was quenched by these three flavonoids via a static process. All the interactions were moderate and the main driving forces are hydrophobic (ΔH > 0 and ΔS > 0) for rutin and luteolin binding or electrostatic (ΔH < 0 and ΔS > 0) for apigenin binding. FRET and molecular docking studies confirm the fluorescence static quenching mechanism by flavonoid binding. The binding of all three flavonoids increases HST stability. These results present the potential use of HST in target-oriented delivery of flavonoids and possibly other drugs into cells.

Transbilayer pores induced by thickness fluctuations.

Thermally-induced fluctuations of individual phospholipids in a bilayer lipid membrane (BLM) are converted into collective motions due to the intermolecular interactions. Here, we demonstrate that transbilayer stochastic pores can be generated via collective thermal movements (CTM). Using the elastic theory of continuous media applied to smectic-A liquid crystals, we estimate the pore radius and the energetic requirements for pore appearance. Three types of thermally-induced transbilayer pores could be formed through BLMs: open and stable, open and unstable, and closed. In most of the situations, two open and stable pores with different radii could be generated. Notably, the two pores have the same generation probability. Unstable pores are possible to appear across thin bilayers that contain phospholipids with a large polar headgroup. Closed pores are present throughout the cases that we have inspected. The effects of hydrophobic thickness, polar headgroup size of phospholipids, temperature, surface tension, and elastic compression on the pore formation and pore stability have been examined as well.