6 research outputs found
Rational in silico design of aptamers for organophosphates based on the example of paraoxon
The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Poisoning by organophosphates (OPs) takes one of the leading places in the total
number of exotoxicoses. Detoxication of OPs at the first stage of the poison entering the
body could be achieved with the help of DNA- or RNA-aptamers, which are able to
bind poisons in the bloodstream. The aim of the research was to develop an approach to
rational in silico design of aptamers for OPs based on the example of paraoxon. From
the published sequence of an aptamer binding organophosphorus pesticides, its threedimensional
model has been constructed. The most probable binding site for paraoxon
was determined by molecular docking and molecular dynamics (MD) methods. Then
the nucleotides of the binding site were mutated consequently and the values of free
binding energy have been calculated using MD trajectories and MM-PBSA approach.
On the basis of the energy values, two sequences that bind paraoxon most efficiently
have been selected. The value of free binding energy of paraoxon with peripheral
anionic site of acetylcholinesterase (AChE) has been calculated as well. It has been
revealed that the aptamers found bind paraoxon more effectively than AChE. The
peculiarities of paraoxon interaction with the aptamers nucleotides have been analyzed.
The possibility of improving in silico approach for aptamer selection is discussed
The universal soldier: enzymatic and non-enzymatic antioxidant functions of serum albumin.
open access articleAs a carrier of many biologically active compounds, blood is exposed to oxidants to a
greater extent than the intracellular environment. Serum albumin plays a key role in antioxidant
defence under both normal and oxidative stress conditions. This review evaluates data published
in the literature and from our own research on the mechanisms of the enzymatic and
nonâenzymatic activities of albumin that determine its participation in redox modulation of plasma
and intercellular fluid. For the first time, the results of numerous clinical, biochemical,
spectroscopic and computational experiments devoted to the study of allosteric modulation of the
functional properties of the protein associated with its participation in antioxidant defence are
analysed. It has been concluded that it is fundamentally possible to regulate the antioxidant
properties of albumin with various ligands, and the binding and/or enzymatic features of the
protein by changing its redox status. The perspectives for using the antioxidant properties of
albumin in practice are discussed
Serum albumin binding and esterase activity: mechanistic interactions with organophosphates
open access articleThe albumin molecule, in contrast to many other plasma proteins, is not covered with a carbohydrate moiety and can bind and transport various molecules of endogenous and exogenous origin. The enzymatic activity of albumin, the existence of which many scientists perceive skeptically, is much less studied. In toxicology, understanding the mechanistic interactions of organophosphates with albumin is a special problem, and its solution could help in the development of new types of antidotes. In the present work, the history of the issue is briefly examined, then our in silico data on the interaction of human serum albumin with soman, as well as comparative in silico data of human and bovine serum albumin activities in relation to paraoxon, are presented. Information is given on the substrate specificity of albumin and we consider the possibility of its affiliation to certain classes in the nomenclature of enzymes