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 Zn(2+)
ions were substituted by Al(3+)
ions. To analyze the stability of Al(3+)
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.