Molecular Docking, Metal Substitution and Hydrolysis Reaction of Chiral Substrates of Phosphotriesterase
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18450%2F16%3A50004719" target="_blank" >RIV/62690094:18450/16:50004719 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.2174/1386207319666160325113844" target="_blank" >http://dx.doi.org/10.2174/1386207319666160325113844</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.2174/1386207319666160325113844" target="_blank" >10.2174/1386207319666160325113844</a>
Alternative languages
Result language
angličtina
Original language name
Molecular Docking, Metal Substitution and Hydrolysis Reaction of Chiral Substrates of Phosphotriesterase
Original language description
During World War II, organophosphorus compounds with neurotoxic action were developed and used as the basis for the development of structures currently used as pesticides in the agricultural industry. Among the nerve agents, Tabun, Sarin, Soman and VX are the most important. The factor responsible for the high toxicity of organophosphorus (OP) is the acetylcholinesterase inhibition. However, one of the characterized enzymes capable of degrading OP is Phosphotriesterase (PTE). This enzyme has generated considerable interest for applications of rapid and complete detoxification. Due to the importance of bioremediation methods for the poisoning caused by OP, this work aims to study the interaction mode between the PTE enzyme and organophosphorus compounds, in this case, Sarin, Soman, Tabun and VX have been used, which are potent acetylcholinesterase inhibitors, taking into account the enantiomers "Rp" and " Sp" of each compound, with the Sp-enantiomers presenting the higher toxicity. With that, we were able to demonstrate the existence of the stereochemical preference by PTE in these compounds. With the purpose of increasing the speed of the hydrolysis mechanism, we have proposed a modification in the enzyme active site structure, where Zn2+ ions were substituted by Al3+ ions. To analyze the stability of Al3+ ions in the wild-type PTE active site, MD simulations were also performed. This mutation brought relevant results; in this case, there was a reduction of the reaction energy barrier for all the compounds, mainly for VX in which the reaction presented lower activation energy values, and consequently, a faster hydrolysis process.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10609 - Biochemical research methods
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Combinatorial chemistry and high throughput screening
ISSN
1386-2073
e-ISSN
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Volume of the periodical
19
Issue of the periodical within the volume
4
Country of publishing house
AE - UNITED ARAB EMIRATES
Number of pages
11
Pages from-to
334-344
UT code for WoS article
000378053300010
EID of the result in the Scopus database
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