Catalytic Characteristics of New Antibacterials Based on Hexahistidine-Containing Organophosphorus Hydrolase

Abstract

Catalytic characteristics of hexahistidine-containing organophosphorus hydrolase (His 6 -OPH) and its enzyme-polyelectrolyte complexes with poly-L-glutamic acid or poly-L-aspartic acid (His 6 -OPH/PLD 50 ), hydrolyzing organophosphorous compounds, and N-acyl homoserine lactones were studied in the presence of various antibiotics (ampicillin, gentamicin, kanamycin, and rifampicin). The antibiotics at concentrations below 1 g·L −1 had a negligible inhibiting effect on the His 6 -OPH activity. Mixed inhibition of His 6 -OPH was established for higher antibiotic concentrations, and rifampicin was the most potent inhibitor. Stabilization of the His 6 -OPH activity was observed in the presence of antibiotics at a concentration of 0.2 g·L −1 during exposure at 25-41 • C. Molecular docking of antibiotics to the surface of His 6 -OPH dimer revealed the antibiotics binding both to the area near active centers of the enzyme subunits and to the region of contact between subunits of the dimer. Such interactions between antibiotics and His 6 -OPH were verified with Fourier-transform infrared (FTIR) spectroscopy. Considering all the results of the study, the combination of His 6 -OPH/PLD 50 with β-lactam antibiotic ampicillin was established as the optimal one in terms of exhibition and persistence of maximal lactonase activity of the enzyme.

Enzymes for Detoxification of Various Mycotoxins: Origins and Mechanisms of Catalytic Action

“…Aflatoxin dialdehyde aldo-keto reductase AKR7A1 (Figure 2 [15,16], Table 1 [17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58]) was isolated from rat liver, and its structure in complex with NADP + was solved [59]. This enzyme is assumed to reduce both aldehyde groups of dialdehyde of hydroxy aflatoxin B 2a , forming from 8,9-dihydrodiol aflatoxin B 1 , resulted in dihydroxy derivative.…”

“…Position and geometry of substrate binding was determined using molecular docking with Autodock Vina as described [15] (see Appendix A for details). Molecular surface of substrate was calculated using Gamess-US as described [16] and is shown as mesh. Within reaction scheme, OH-groups marked with blue are introduced by cytochromes, and oxygens marked with red are modified by AKR7A1.…”

Biocatalysis and Biotransformations

“…Similarly, Huang and coworkers design selenium-containing trypsin mimics that increase the substrate binding capacity and stability of glutathione peroxidases [34]. Maslova and coworkers investigated how lactonase activity of organophosphorus hydrolases can be increased by producing enzyme-polyelectrolyte complexes with poly-L-glutamic acid or poly-L-aspartic acid and adding small concentrations of antibiotics [35].…”

Simultaneous molecular docking of different ligands to His6-tagged organophosphorus hydrolase as an effective tool for assessing their effect on the enzyme

“…Hexahistidine-tagged organophosphorus hydrolase (His 6 -OPH) is one such enzyme. It was previously shown that His 6 -OPH, in addition to its high catalytic activity in the process of hydrolysis of a number of organophosphorous compounds, also has lactonase activity against a number of AHLs (Maslova et al, 2017a; Maslova et al, 2017b). It has been established that combinations of His 6 -OPH with β-lactam antibiotics provide an increase in the efficiency of action of both the enzyme and antibiotics (Maslova et al, 2017a; Maslova et al, 2017b; Aslanli, Lyagin & Efremenko, 2018).…”

“…It was previously shown that His 6 -OPH, in addition to its high catalytic activity in the process of hydrolysis of a number of organophosphorous compounds, also has lactonase activity against a number of AHLs (Maslova et al, 2017a; Maslova et al, 2017b). It has been established that combinations of His 6 -OPH with β-lactam antibiotics provide an increase in the efficiency of action of both the enzyme and antibiotics (Maslova et al, 2017a; Maslova et al, 2017b; Aslanli, Lyagin & Efremenko, 2018). These results reinforce the interest in studying the possibility of combining His 6 -OPH with other antibiotics characterized by different chemical properties and a spectrum of bacterial targets (Azzam & Algranati, 1973; Salmon, Watts & Yancey Jr, 1996).…”