Asymmetric biocatalysis of the nerve agent VX by human serum paraoxonase 1: Molecular Docking and Reaction Mechanism calculations

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18450%2F16%3A50005093" target="_blank" >RIV/62690094:18450/16:50005093 - isvavai.cz</a>

Výsledek na webu

<a href="https://link.springer.com/article/10.1007/s00044-016-1704-x" target="_blank" >https://link.springer.com/article/10.1007/s00044-016-1704-x</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00044-016-1704-x" target="_blank" >10.1007/s00044-016-1704-x</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Asymmetric biocatalysis of the nerve agent VX by human serum paraoxonase 1: Molecular Docking and Reaction Mechanism calculations

Popis výsledku v původním jazyce

Organophosphorus compounds have been employed in agricultural activity for a long time, causing serious public health problems. Due to their toxic properties, these compounds have also been used as chemical weapons. In view of this scenario, the catalytic degradation and the development of bioremediation processes of organophosphorus compounds have been of wide interest. Among several enzymes capable of degrading organophosphorus compounds, the human serum paraoxonase 1 has shown good potential for this purpose. To evaluate the interaction mode between the human serum paraoxonase 1 (wild-type and mutants) enzymes and the VX compound, one of the most toxic organophosphorus compounds known, molecular docking calculations were conducted. In addition, seeking to analyze the reaction pathway and the stereochemistry preference by human serum paraoxonase 1 and the Rp and Sp enantiomers of VX, quantum mechanical/molecular mechanics calculations were performed. Our theoretical findings put in evidence that the wild-type and mutant human serum paraoxonase 1 enzymes strongly interact with VX. Moreover, with the quantum mechanical/molecular mechanics study, we observed that the human serum paraoxonase 1 preferentially degrades one enantiomer in relation to the other. The current results indicate key points for designing new, more efficient mutant human serum paraoxonase 1 enzymes for VX degradation.

Název v anglickém jazyce

Asymmetric biocatalysis of the nerve agent VX by human serum paraoxonase 1: Molecular Docking and Reaction Mechanism calculations

Popis výsledku anglicky

Organophosphorus compounds have been employed in agricultural activity for a long time, causing serious public health problems. Due to their toxic properties, these compounds have also been used as chemical weapons. In view of this scenario, the catalytic degradation and the development of bioremediation processes of organophosphorus compounds have been of wide interest. Among several enzymes capable of degrading organophosphorus compounds, the human serum paraoxonase 1 has shown good potential for this purpose. To evaluate the interaction mode between the human serum paraoxonase 1 (wild-type and mutants) enzymes and the VX compound, one of the most toxic organophosphorus compounds known, molecular docking calculations were conducted. In addition, seeking to analyze the reaction pathway and the stereochemistry preference by human serum paraoxonase 1 and the Rp and Sp enantiomers of VX, quantum mechanical/molecular mechanics calculations were performed. Our theoretical findings put in evidence that the wild-type and mutant human serum paraoxonase 1 enzymes strongly interact with VX. Moreover, with the quantum mechanical/molecular mechanics study, we observed that the human serum paraoxonase 1 preferentially degrades one enantiomer in relation to the other. The current results indicate key points for designing new, more efficient mutant human serum paraoxonase 1 enzymes for VX degradation.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Medicinal chemistry research

ISSN

1054-2523

e-ISSN

—

Svazek periodika

25

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

2521-2533

Kód UT WoS článku

000386763500009

EID výsledku v databázi Scopus

2-s2.0-84981205697