Effect of Bovine Serum Albumin Redox Status on Its Interaction with Paraoxon as Determined by Molecular Modeling
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RIMENTAL PAPERS
Effect of Bovine Serum Albumin Redox Status on Its Interaction with Paraoxon as Determined by Molecular Modeling D. A. Belinskaiaa,*, A. A. Batalovaa, and N. V. Goncharova,b a
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia bResearch
Institute of Hygiene, Occupational Pathology and Human Ecology, St. Petersburg, Russia *email: [email protected] Received December 7, 2019 Revised January 5, 2020 Accepted January 20, 2020
DOI: 10.1134/S0022093020050063 Abbreviations: OP—organophosphate; BSA—bovine serum albumin; HSA—human serum albumin; MMPBSA—Molecular Mechanics–Poisson–Boltzmann Surface Area (an approach to estimate the binding free energy of small ligands to biological macromolecules); distPO—the distance between the paraoxon phosphorous atom and the Tyr149 or Tyr410 hydroxyl oxygen atom
Albumin is a major protein of mammalian blood plasma. It maintains its colloid osmotic (oncotic) pressure, performs a reserve function, plays an important role in the transport of water, ions and various compounds. There is an increas ing body of evidence for the enzymatic activity of albumin: true esterase activity (substrate binding to the albumin active center with subsequent dis sociation of the complex into the protein and enzyme constituents) and pseudoesterase activity (irreversible substrat–enzyme binding). The two major sites for hydrolytic activity of the protein have been identified. Sudlow site I with a catalytic amino acid residue Tyr150 is responsible for the true esterase activity of albumin, while Sudlow site II with a catalytic amino acid residue Tyr 411
is in charge of the pseudoesterase activity. The hydrolytic activity of albumin towards some organophosphates (OPs) has also been established [1]. The 3D structure of albumin is quite labile and allows a cooperativity and allosteric modulation when interacting with various substances, which are typically inherent to multimeric proteins. The albumin molecule contains a single free thiol group within the Cys34 residue, which is able to form disulfides with free cysteine and other plasma thiols or oxidize to sulfenic and sulfinic acids [1]. The effect of the degree of Cys34 oxida tion on binding and catalytic properties of albu min has not been actually investigated, while the outcomes of the studies devoted to this issue are
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EFFECT OF BOVINE SERUM ALBUMIN REDOX STATUS
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Fig. 1. Stable paraoxon conformations at Sudlow site I (a, b, c) and Sudlow site II (d, e, f) of bovine serum albumin with dif ferent oxidation degrees of the Cys34 thiol group: (a, d) Cys34 reduced; (b, e) Cys34 oxidized to sulfenic acid; (c, f) Cys34 oxi dized to sulfinic acid.
ambiguous. The aim of this work was to assess the influence of the degree of Cys34 oxidation on the binding and (pseudo)esterase activities of bovine serum albumin (BSA) towards OPs and to com pare the obtained data with the results of our pre vious identical study carried out on human serum albumin (HSA). The thr
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