Organophosphorus Neurotoxins

Abstract

The collective monograph is devoted to discussing the history of creation, studying the properties, neutralizing and using organophosphorus neurotoxins, which include chemical warfare agents, agricultural crop protection chemical agents (herbicides and insecticides) and medicines. The monograph summarizes the results of current scientific research and new prospects for the development of this field of knowledge in the 21st century, including the use of modern physicochemical methods for experimental study and theoretical analysis of biocatalysis and its mechanisms based on molecular modeling with supercomputer power. 
 The book is intended for specialists who are interested in the current state of research in the field of organophosphorus neurotoxins. The monograph will be useful for students, graduate students, researchers specializing in the field of physical chemistry, physicochemical biology, chemical enzymology, toxicology, biochemistry, molecular biology and genetics, biotechnology, nanotechnology and biomedicine.

Enzymes, Reacting with Organophosphorus Compounds as Detoxifiers: Diversity and Functions

“…OPH was firstly isolated from bacterial cells of Pseudomonas diminuta (currently classified as Brevundimonas diminuta) and Flavobacterium sp. which were extracted from a soil contaminated with parathion [1]. Hundreds of other enzymes having a high identity (i.e., the extent to which two amino acid sequences have the same residues at the same positions in an alignment and are expressed as a percentage) with OPH (Figure 2) were subsequently found in the genetic material of a wide variety of microorganisms, and are now grouped in a separate family of Phosphotriesterase-like lactonases (PLLs).…”

“…The active center is assembled at the C-terminus of the β-barrel and contains two divalent metal ions. Zn 2+ ions were found in the native OPH but the enzyme is fully active with Cd 2+ , Mn 2+ , and Ni 2+ [1], and the maximal activity is observed with Co 2+ [10]. The coordination sphere of the more buried α-metal ion includes two amino acid residues of histidine (His55 and His57 from β-strand 1) and aspartic acid (Asp301 from β-strand 8) and has a trigonal bipyramidal geometry (Scheme 1).…”

“…β-metal ion is slightly more exposed to the solvent and surrounded by two histidines (His201 from β-sheet 5 and His230 from β-strand 6) which form an octahedral coordination sphere together with other amino acid residues and bound water molecules. The two metals are bridged by a water molecule (or hydroxyl-ion) and carboxylated lysine (Lys169 from β-strand 4), formed as a result of the interaction of Lys169 with CO 2 dissolved in water [1]. Paraoxon is the best substrate for OPH, and the catalytic efficacy of its hydrolysis is close to the diffusion limit from the solvent, although the enzyme can also act on substrates with hydrolyzable P-O, P-F, P-S, and C-P bonds [11].…”

“…Another enzyme being active towards OPCs is organophosphorus acid anhydrolase (OPAA) from bacteria Alteromonas sp. [1]. OPAA belongs to prolidases (a superfamily of aminopeptidases).…”

“…Organophosphorus compounds (OPCs) are extremely dangerous and have a wide variety of chemical structures mainly presented by phosphotriester, thiophosphotriester, and phosphorothioester moieties [1]. Pesticides currently approved for application among OPCs contain sulfur instead of phosphoryl oxygen.…”