Effect of Cys34 Oxidation State of Albumin on Its Interaction with Paraoxon according to Molecular Modeling Data

The Universal Soldier: Enzymatic and Non-Enzymatic Antioxidant Functions of Serum Albumin

“…The latter substitutions are of particular interest since His242(His241) and His288(His287) are located in very close proximity to the catalytic tyrosine Tyr150(Tyr149). According to our computational experiments [ 70 , 71 , 72 , 73 ], the imidazole ring of His242(241) can attract the proton of the hydroxyl group of Tyr150(Tyr149) and thus regulate the hydrolytic activity of the tyrosine. It should be expected that interspecies differences in the binding and catalytic properties of albumin will show themselves in the characteristics of Sudlow site I.…”

“…However, the most remarkable difference is that Tyr140(Tyr139) in HSA and BSA is replaced with His140 in RSA. Previously, we showed that Sudlow site I and the redox site of HSA and BSA have a mutual effect on each other: a change in the conformation of one site leads to conformational changes in the other [ 73 , 74 ]. In the redox site, the amino acid residues Cys34, His39, Tyr140(Tyr139) and Arg144(Arg143) and their mutual arrangement (the -SH groups of the cysteine and the -OH groups of the tyrosine relative to the imidazole ring of His39, as well as the -OH group of the tyrosine relative to the side chain of Arg144(Arg143)) play the main role in this effect.…”

“…We now review the effect of Cys34 oxidation on albumin binding and pseudo(esterase) activity. Our own computational experiments, performed as a part of investigation of the interaction of albumin with OPs, were devoted to the study of the influence of the redox status of HSA on their interaction with paraoxon [ 73 ]. We tested three models of the oxidation state of albumin: Cys34 is reduced (Cys34-SH), Cys34 is oxidised to sulfenic acid (Cys34-SOH) and Cys34 is oxidised to sulfinic acid (Cys34-S(O)O − ).…”

“…The change in the shape of the spectrum in the regions 8.2–7.5 ppm and 7.1–6.9 ppm reflects the change in signals from C ε H and C γ H 2 groups of histidines, respectively [ 128 , 129 , 132 ]. The appearance of a weak signal d and a decrease in the intensity of h’ peak in oxBSA probably indicates a change in the conformation of His39, which interacts with the SH-group of Cys34 in reduced but not in oxidised albumin [ 73 , 74 ]. Stewart et al also noted the importance of His39 in the reactivity of the thiol group of Cys34 [ 133 ].…”

“…In our recent computational experiments [ 73 ], we have analysed how the redox status of HSA affects the binding of paraoxon in Sudlow sites I and II. However, an analysis of the effect of paraoxon binding on the conformation of Cys34 and its microenvironment has not been performed.…”