Analyzing organophosphate pesticide-serum albumin binding interaction: a combined STD NMR and molecular docking study
24 Mar 2021-Journal of Biomolecular Structure & Dynamics (Taylor & Francis)-Vol. 39, Iss: 5, pp 1865-1878
TL;DR: In Vitro analysis of the interaction of organophosphate pesticides (OP) with bovine serum albumin (BSA) is crucial to understand their potential effects at the molecular level and Saturation Transfer Difference NMR experiments in conjunction with molecular docking studies revealed a high binding affinity of OP-BSA complexes through non-covalent interaction.
Abstract: In Vitro analysis of the interaction of organophosphate pesticides (OP) with bovine serum albumin (BSA) is crucial to understand their potential effects at the molecular level. In this context, we ...
Citations
More filters
TL;DR: In this article, a review of OPC-based enzymes is presented, including their structural differences and identity, mechanisms, and specificity of catalytic action, including results of computational modeling.
Abstract: Organophosphorus compounds (OPCs) are able to interact with various biological targets in living organisms, including enzymes. The binding of OPCs to enzymes does not always lead to negative consequences for the body itself, since there are a lot of natural biocatalysts that can catalyze the chemical transformations of the OPCs via hydrolysis or oxidation/reduction and thereby provide their detoxification. Some of these enzymes, their structural differences and identity, mechanisms, and specificity of catalytic action are discussed in this work, including results of computational modeling. Phylogenetic analysis of these diverse enzymes was specially realized for this review to emphasize a great area for future development(s) and applications.
12 citations
TL;DR: The experimental and computational results have provided the binding affinity, binding mode, conformational flexibility, and thermodynamic profile of Formetanate Hydrochloride (FMT)-HSA complex as mentioned in this paper .
6 citations
TL;DR: In this paper, the role of intermolecular interactions, specifically halogen and chalcogen bonds, in EDC recognition processes is discussed, with an overview of the latest advances in the study of disruption mechanisms.
Abstract: Endocrine-disrupting chemicals (EDCs) are natural or synthetic substances able to mimic, interfere with, or block endogenous hormones, thus disrupting the normal function of the endocrine system Most of them are largely applied in agriculture and industry As a result, humans are chronically exposed to mixtures of EDCs Their adverse effect on human health may appear long after exposure, making it difficult to assess their full impact Thus, understanding the molecular basis of recognition of suspected EDCs by their biological targets is fundamental to get insight into their mechanism of action This review will focus on the role of intermolecular interactions, specifically halogen and chalcogen bonds, in EDC recognition processes, offering an overview of the latest advances in the study of disruption mechanisms
6 citations
TL;DR: A modern view on the molecular pathophysiological mechanisms of acute nephrotoxicity of organophosphate compounds is presented.
Abstract: Organophosphates (OPs) are toxic chemicals produced by an esterification process and some other routes. They are the main components of herbicides, pesticides, and insecticides and are also widely used in the production of plastics and solvents. Acute or chronic exposure to OPs can manifest in various levels of toxicity to humans, animals, plants, and insects. OPs containing insecticides were widely used in many countries during the 20th century, and some of them continue to be used today. In particular, 36 OPs have been registered in the USA, and all of them have the potential to cause acute and sub-acute toxicity. Renal damage and impairment of kidney function after exposure to OPs, accompanied by the development of clinical manifestations of poisoning back in the early 1990s of the last century, was considered a rare manifestation of their toxicity. However, since the beginning of the 21st century, nephrotoxicity of OPs as a manifestation of delayed toxicity is the subject of greater attention of researchers. In this article, we present a modern view on the molecular pathophysiological mechanisms of acute nephrotoxicity of organophosphate compounds.
4 citations
TL;DR: In this article, the authors used proton nuclear magnetic resonance (1H NMR) to study the true esterase activity of albumin, using the example of bovine serum albumin (BSA) and p-nitrophenyl acetate (NPA).
Abstract: Serum albumin possesses esterase and pseudo-esterase activities towards a number of endogenous and exogenous substrates, but the mechanism of interaction of various esters and other compounds with albumin is still unclear. In the present study, proton nuclear magnetic resonance (1H NMR) has been applied to the study of true esterase activity of albumin, using the example of bovine serum albumin (BSA) and p-nitrophenyl acetate (NPA). The site of BSA esterase activity was then determined using molecular modelling methods. According to the data obtained, the accumulation of acetate in the presence of BSA in the reaction mixture is much more intense as compared with the spontaneous hydrolysis of NPA, which indicates true esterase activity of albumin towards NPA. Similar results were obtained for p-nitophenyl propionate (NPP) as substrate. The rate of acetate and propionate release confirms the assumption that there is a site of true esterase activity in the albumin molecule, which is different from the site of the pseudo-esterase activity Sudlow II. The results of molecular modelling of BSA and NPA interaction make it possible to postulate that Sudlow site I is the site of true esterase activity of albumin.
1 citations
References
More filters
TL;DR: This experiment is ideal to illustrate some fundamental NMR concepts, such as the nuclear Overhauser effect and relaxation in a multidisciplinary context, bridging chemistry and biochemistry with a taste of medicinal chemistry.
Abstract: Saturation transfer difference (STD) NMR has emerged as one of the most popular ligand-based NMR techniques for the study of protein−ligand interactions. The success of this technique is a consequence of its robustness and the fact that it is focused on the signals of the ligand, without any need of processing NMR information about the receptor and only using small quantities of nonlabeled macromolecule. Moreover, the attractiveness of this experiment is also extendable to the classroom. In the context of a practical NMR class, this experiment is ideal to illustrate some fundamental NMR concepts, such as the nuclear Overhauser effect and relaxation in a multidisciplinary context, bridging chemistry and biochemistry with a taste of medicinal chemistry.We use the readily available human serum albumin (HSA), 6-d,l-methyl-tryptophan (6-CH3-Trp), and 7- d,l-methyl-tryptophan (7-CH3-Trp) to introduce the STD-NMR experiment and to illustrate its applicability for ligand screening, mapping of binding moieties, an...
244 citations
TL;DR: Chlorpyrifos, previously shown to be resistant to enhanced degradation, has now been proved to undergo enhanced microbe-mediated decay and special emphasis is given to degradation methods such as ozonation, Fenton treatment, photodegradation, and advanced oxidation processes along with microbial degradation.
Abstract: The widespread use of pesticides in modern agriculture is of increasing concern due to environmental contamination and subsequent biodiversity loss. Chlorpyrifos is a toxic organophosphate pesticide. Repeated applications of chlorpyrifos modify the soil microbial community structure and pose potential health risks to the other nontargets. Chlorpyrifos has been reported as the second most commonly detected pesticide in food and water. Extensive use of chlorpyrifos in agriculture and persistence in the environment have raised public concern and demand for safe technologies to overcome the pollution and toxicity problems. Here, we review pollution and toxicity issues associated with chlorpyrifos use and discuss strategies to solve pesticide contamination. Chlorpyrifos, previously shown to be resistant to enhanced degradation, has now been proved to undergo enhanced microbe-mediated decay. Here, special emphasis is given to degradation methods such as ozonation, Fenton treatment, photodegradation, and advanced oxidation processes along with microbial degradation. Finally, we focus on degradation process at enzyme and molecular levels which will enable us to elucidate the exact degradative pathway involved in biodegradation.
204 citations
TL;DR: Results suggest that the primary binding site for methyl parathion on albumin is close to tryptophan residues 214 of human serum albumin and 212 of bovine serum albumIn, and suggest that this pesticide is potentially toxic for both vertebrates and invertebrates.
204 citations
TL;DR: The fluorescence spectra revealed that CPF causes the quenching of the fluorescence emission of serum albumin, and the alterations of protein secondary structure in the presence of CPF were confirmed by the evidences from UV and CD spectra.
Abstract: Chlorpyrifos (CPF) is a widely used organophosphate insecticide which could bind with human serum albumin (HSA) and bovine serum albumin (BSA). The binding behavior was studied employing fluorescence, three-dimensional fluorescence, Circular dichroism (CD) spectroscopy, UV-vis absorption spectroscopy, electrochemistry and molecular modeling methods. The fluorescence spectra revealed that CPF causes the quenching of the fluorescence emission of serum albumin. Stern-Volmer plots were made and quenching constants were thus obtained. The results suggested the formation of the complexes of CPF with serum albumins, which were in good agreement with the results from electrochemical experiments. Association constants at 25°C were 3.039 × 10(5) mol L(-1) for HSA, and 0.3307 × 10(5) mol L(-1) for BSA, which could affect the distribution, metabolism, and excretion of pesticide. The alterations of protein secondary structure in the presence of CPF were confirmed by the evidences from UV and CD spectra. Site competitive experiments also suggested that the primary binding site for CPF on serum albumin is close to tryptophan residues 214 of HSA and 212 of BSA, which was further confirmed by molecular modeling.
165 citations
TL;DR: It is demonstrated that the effects of these factors are cancelled out by analyzing the protein-ligand association curve using STD values at the limit of zero saturation time, when virtually no ligand rebinding or relaxation takes place.
Abstract: The direct evaluation of dissociation constants (K(D)) from the variation of saturation transfer difference (STD) NMR spectroscopy values with the receptor-ligand ratio is not feasible due to the complex dependence of STD intensities on the spectral properties of the observed signals. Indirect evaluation, by competition experiments, allows the determination of K(D), as long as a ligand of known affinity is available for the protein under study. Herein, we present a novel protocol based on STD NMR spectroscopy for the direct measurements of receptor-ligand dissociation constants (K(D)) from single-ligand titration experiments. The influence of several experimental factors on STD values has been studied in detail, confirming the marked impact on standard determinations of protein-ligand affinities by STD NMR spectroscopy. These factors, namely, STD saturation time, ligand residence time in the complex, and the intensity of the signal, affect the accumulation of saturation in the free ligand by processes closely related to fast protein-ligand rebinding and longitudinal relaxation of the ligand signals. The proposed method avoids the dependence of the magnitudes of ligand STD signals at a given saturation time on spurious factors by constructing the binding isotherms using the initial growth rates of the STD amplification factors, in a similar way to the use of NOE growing rates to estimate cross relaxation rates for distance evaluations. Herein, it is demonstrated that the effects of these factors are cancelled out by analyzing the protein-ligand association curve using STD values at the limit of zero saturation time, when virtually no ligand rebinding or relaxation takes place. The approach is validated for two well-studied protein-ligand systems: the binding of the saccharides GlcNAc and GlcNAcbeta1,4GlcNAc (chitobiose) to the wheat germ agglutinin (WGA) lectin, and the interaction of the amino acid L-tryptophan to bovine serum albumin (BSA). In all cases, the experimental K(D) measured under different experimental conditions converged to the thermodynamic values. The proposed protocol allows accurate determinations of protein-ligand dissociation constants, extending the applicability of the STD NMR spectroscopy for affinity measurements, which is of particular relevance for those proteins for which a ligand of known affinity is not available.
160 citations