Experimental and computational studies on the binding of diazinon to human serum albumin

Abstract

In the present research, the binding properties of diazinon (DZN), as an organophosphorus herbicide, to human serum albumin (HSA) were investigated using combination of spectroscopic, electrochemistry, and molecular modeling techniques. Changes in the UV-Vis and FT-IR spectra were observed upon ligand binding along with a significant degree of tryptophan fluorescence quenching on complex formation. The obtained results from spectroscopic and electrochemistry experiments along with the computational studies suggest that DZN binds to residues located in subdomains IIA of HSA with binding constant about 1410.9 M at 300 K. From the thermodynamic parameters calculated according to the van't Hoff equation, the enthalpy change ΔH° and entropy change ΔS° were found to be -16.695 and 0.116 KJ/mol K, respectively. The primary binding pattern is determined by hydrophobic interaction and hydrogen binding occurring in so-called site I of HSA. DZN could slightly alter the secondary structure of HSA. All of experimental results are supported by computational techniques such as docking and molecular dynamics simulation using a HSA crystal model.

Molecular Assessment of the Toxic Mechanism of the Latest Neonicotinoid Dinotefuran with Glutathione Peroxidase 6 from Arabidopsis thaliana

“…The fluorescence quenching of proteins is usually attributed to a variety of molecular interactions including excited-state reactions, energy transfer, ground-state complex formation, and collisional quenching. The intrinsic fluorescence of AtGPX6 is mainly derived from the tryptophan and tyrosine residues . The fluorescence emission spectra of AtGPX6 with the gradual addition of dinotefuran were collected.…”

Elucidating the interaction of letrozole with human serum albumin by combination of spectroscopic and molecular modeling techniques

“…These results indicated that there were interactions between LET and HSA and the binding reactions resulted in non-fluorescent complex( 26 ). The regular decrease of emission signal of the protein without changing the shape of the peaks may imply that the tryptophan residue should be located at or near the drug-binding site( 7 8 9 10 30 34 ). The results of Stern-Volmer plot indicated that the value of K sv decreased with increasing temperature in the presence of LET demonstrating that the quenching mechanism is static.…”

“…The kq values are greater than the maximum scatter collision quenching indicating that the quenching mechanism involved in the LET-HSA system was initiated by static rather than dynamic quenching process( 48 ). The value of K b is significant to understand the distribution of the drug in plasma since the weak binding can lead to a short lifetime or poor distribution, while strong binding can decrease the concentration of free drug in plasma( 7 8 9 10 ). Since the K b value for the LET-HSA system was found to be in the range of 1.70-1.25 × 10 4 M −1 , a moderate binding affinity between LET and has could be assumed.…”

“…Human serum albumin is a helical protein with a heart shape tertiary structure and approximate dimensions of 8 × 8 × 3 nm. It consists of three domains: domain I (residues 1-195), II (residues 196-383), and III (384-585) and in each domain there are two subdomains (A and B), and 17 disulfide bridges stabilizing the whole protein structure( 7 8 9 10 11 ).…”

Insights from a combination of theoretical and experimental methods for probing the biomolecular interactions between human serum albumin and clomiphene

“…11,12 HSA is a non-glycosylated and singlechain protein comprising 585 amino acids, with a molecular weight of 66 500 Da. [13][14][15] HSA has various physiological functions including contributing to colloid osmotic blood pressure and acting as a carrier, distributor and metabolizing agent for many metabolites and molecules such as drugs, fatty acids, hormones, cations and anions, and amino acids. 16 It is known that the binding of drugs to HSA alters their free concentration, distribution and metabolism.…”