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: Some of these issues have been debated and studied for some time, while others are newer, suggesting that the study of the toxicology of OPs will remain an important scientific and public health issue for years to come.
146 citations
TL;DR: The objective of this article is to review the current status of this powerful NMR technique, with particular emphasis on quantitative applications, within the framework of the (bio-)chemistry of molecular recognition.
Abstract: Saturation transfer difference NMR (STD NMR) spectroscopy is one of the most powerful NMR techniques for detection and characterization of transient (fast) receptor–ligand interactions in solution. By observing the signals of a small molecule (ligand) with spectroscopic properties suitable for high-resolution studies, irrespective of receptor size, STD NMR enables quantitative structural and affinity information to be obtained about the molecular recognition process under study. Approximately one decade after its introduction, the technique has reached maturity, and is highly robust and useful. The objective of this article is to review the current status of this powerful technique, with particular emphasis on quantitative applications, within the framework of the (bio-)chemistry of molecular recognition.
134 citations
TL;DR: It can be used for compound library screening against a broad range of drug targets to identify both high‐ and low‐affinity ligands and to rank order analogs rapidly and derive structure–activity relationships, which are used to optimize these NMR hits into viable drug leads.
Abstract: The reported competition STD NMR method combines saturation transfer difference (STD) NMR with competition binding experiments to allow the detection of high-affinity ligands that undergo slow chemical exchange on the NMR time-scale. With this technique, the presence of a competing high-affinity ligand in the compound mixture can be detected by the disappearance or reduction of the STD signals of a low-affinity indicator ligand. This is demonstrated on a BACE1 (beta-site amyloid precursor protein cleaving enzyme 1) protein-inhibitor system. This method can also be used to derive an approximate value, or a lower limit, for the dissociation constant of the potential ligand based on the reduction of the signal intensity of the STD indicator, which is illustrated on an HSA (human serum albumin) model system. This leads to important applications of the competition STD NMR method for lead discovery: it can be used (i) for compound library screening against a broad range of drug targets to identify both high- and low-affinity ligands and (ii) to rank order analogs rapidly and derive structure-activity relationships, which are used to optimize these NMR hits into viable drug leads.
129 citations
TL;DR: Three major ligand-observed NMR methods that depend on the nuclear Overhauser effect Spectroscopy, saturation transfer difference spectroscopy and water–ligand interactions observed via gradient spectroscopic experiments are reviewed with the aim of reporting recent developments and applications for the characterization of protein–ligands complexes, including affinity measurements and structural determination.
Abstract: Physiological processes are mainly controlled by intermolecular recognition mechanisms involving protein–protein and protein–ligand (low molecular weight molecules) interactions. One of the most important tools for probing these interactions is high-field solution nuclear magnetic resonance (NMR) through protein-observed and ligand-observed experiments, where the protein receptor or the organic compounds are selectively detected. NMR binding experiments rely on comparison of NMR parameters of the free and bound states of the molecules. Ligand-observed methods are not limited by the protein molecular size and therefore have great applicability for analysing protein–ligand interactions. The use of these NMR techniques has considerably expanded in recent years, both in chemical biology and in drug discovery. We review here three major ligand-observed NMR methods that depend on the nuclear Overhauser effect—transferred nuclear Overhauser effect spectroscopy, saturation transfer difference spectroscopy and water–ligand interactions observed via gradient spectroscopy experiments—with the aim of reporting recent developments and applications for the characterization of protein–ligand complexes, including affinity measurements and structural determination.
120 citations
08 Jul 2015
108 citations