Pesticides are extensively used to control the spread of insects or unwanted weeds. Among various pesticides, organophosporus pesticides are the largest individual group of pesticides, with more than 100 compounds being marketed. Their high effectiveness has resulted in the widespread use throughout the world. Exposure to organophosporus pesticides affects the central nervous system, the autonomic nervous system and peripheral muscular pathways, though the effects associated with these chemicals may be either immediate or delayed. To remove the pesticide residues in nature, enzymatic biodegradation has been recommended in terms of safety and economy. It has been found that an enzyme known as phosphotriesterase (PTE) which is isolated from naturally soil-dwelling bacterium, Pseudomonas diminuta and Flavobacterium sp, can catalyze the hydrolysis of paraoxon to p-nitrophenol and diethyl phosphate. However, PTE does not hydrolyze all the substrates at high rates. We intend to use computational tools to understand the enzymatic mechanism of PTE and further design PTE to enhance its activity towards specific organophosphates and increase its diversity to different organophosphates. Hybrid QM/MM molecular dynamics simulations will be conducted to evaluate the roles of residues in the catalytic pocket and understand the structural origin of the enzyme activity. Further, we plan to engineer the residues in the binding pockets which are computationally redesigned to enhance the reactivity of PTE. The knowledge gained through computational studies will ultimately provide guidelines for experimental tests. ? ?
| Lin, Yuchun; Cao, Zexing; Mo, Yirong (2009) Functional role of Asp160 and the deprotonation mechanism of ammonium in the Escherichia coli ammonia channel protein AmtB. J Phys Chem B 113:4922-9 |
| Zhang, Xin; Wu, Ruibo; Song, Lingchun et al. (2009) Molecular dynamics simulations of the detoxification of paraoxon catalyzed by phosphotriesterase. J Comput Chem 30:2388-401 |
