A novel vision into the binding behavior of curcumin with human serum albumin-holo transferrin complex: molecular dynamic simulation and multi-spectroscopic perspectives.

In this work, we investigated the simultaneous binding of curcumin (CUR) to human serum albumin (HSA) and human-holo transferrin (HTF) in the roles of binary and ternary systems. The binding affinity and binding site of protein-protein interaction were studied by the methods of multiple spectroscopic and molecular dynamics (MD) simulation. According to the results, the measurements for binding constant of HSA-CUR, HTF-CUR and (HSA-HTF) CUR complexes were observed to be 1.51 × 105, 7.93 × 104 and 1.44 × 105 M-1 respectively. Thermodynamic parameters were considered to be set at three varying temperatures including 298, 303, and 308 K. In conformity to the negative values of ΔH0 and ΔS0 the significant roles of hydrogen binding and van der-Waals forces in the formation of complexes are quiet evident. The binding distance between Trp residues of HSA, HTF and HSA-HTF upon interaction with CUR, were acquired by applying the Förster's theory of non-radioactive energy transfer and reported to be 2.04 nm, 1.78 nm, and 1.86 nm, respectively. In accordance with the conductometry and Resonance light scattering (RLS) results, there were different interaction behaviors among the HSA-HTF complex and CUR in ternary system when being compared to the outcomes of binary system. The secondary structure of all three cases increased as the CUR concentration was intensified, which confirmed the inducement of proteins conformational changes through the application of circular dichroism (CD) technique. The experimental results that were acquired throughout the binding of HSA-CUR, HTF-CUR, and (HSA-HTF) CUR complexes were approved by molecular modeling.Communicated by Ramaswamy H. Sarma.

Analysis of the interaction behavior between Nano-Curcumin and two human serum proteins: combining spectroscopy and molecular stimulation to understand protein-protein interaction.

In this study, we have investigated the effects of Nano-curcumin (Nano-CUR) binding on HSA-HTF interactions as binary and ternary systems, which had been done through multiple spectroscopic and MD simulation. It has been indicated by fluorescence spectroscopy that Nano-CUR is capable of quenching both proteins with a static mechanism. Thermodynamic parameters have been calculated by considering the fluorescence data at different temperatures. The binding constants of HSA-Nano-CUR, HTF-Nano-CUR and (HSA-HTF) Nano-CUR complexes formation were (2.03 ± 0.32)×107 M-1, (2.46 ± 0.32)×106 and (4.54 ± 0.32)×106 M-1 respectively. According to the negative values of ΔH0 and ΔS0, the roles of van-der-Waals forces and hydrogen bond are quite essential throughout this particular binding. Besides, the negative ΔH0 and ΔS0 values of HTF (Nano-CUR) have been larger than those of the HSA (Nano-CUR) and HSA-HTF (Nano-CUR), which demonstrates the higher significance of interaction bonding. As it had been detected through the synchronized fluorescence spectroscopy at Δλ = 60 nm, the position of Nano-CUR with mixed protein in ternary system has been closer to Tyr residues. Relatively, the binding distances between Trp residues of HSA and HTF in HSA (Nano-CUR), HTF (Nano-CUR), and (HSA-HTF Nano-CUR) complexes, which had been procured in accordance with the fluorescence resonance energy transfer (FRET), have been found to be 1.82 nm, 1.87 nm, and 1.92 nm, respectively. We have evaluated the induced conformational changes of two proteins throughout the binding of Nano-CUR to HSA and HTF as binary and ternary systems by employing the CD technique, while the formation of self-assemblies has been studied through MD simulation.

Evaluation of NPP1 as a Novel Biomarker of Coronary Artery Disease: A Pilot Study in Human Beings.

Purpose: Coronary artery calcification (CAC) is utilized as an important tool for global risk assessment of cardiovascular events in individuals with intermediate risk. Ecto phosphodiesterase/nucleotide phosphohydrolase-1(ENPP1) converts extracellular nucleotides into inorganic pyrophosphate and it is a key regulator of tissue calcification that adjusts calcification in tissues like vascular smooth muscle cells. The main purpose of this clinical study was to find out the correlation between ENPP1 serum concentration and CAC in human for the first time. Methods: In this study 83 patients (16 diabetic patients and 67 non-diabetic patients) with coronary artery disease who fulfilled inclusion and exclusion criteria, entered the study. For all patients a questionnaire consisting demographic data and traditional cardiovascular risk factors were completed. Computed tomography (CT)-Angiography was carried out to determine coronary artery calcium score and enzyme-linked immunosorbent assay (ELISA) method was used for measuring ENPP1 serum concentrations. Results: There was a reverse significant correlation between ENPP1 serum concentration and total CAC score and also CAC of right coronary artery (RCA) (P<0.05) in non-diabetic patients. Conclusion: On the basis of our results, ENPP1 serum concentration may be a suitable biomarker for coronary artery disease at least in non-diabetic patients. However, more studies with higher sample size are necessary for its confirmation.