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Updated: Apr 13, 2026

Chemical Triphosphorylation of Oligonucleotides
Published on: June 2, 2022
Stereoselectivity of phosphotriesterase with paraoxon derivatives: a computational study
Dongling Zhan1,2, Shanshan Guan3, Hanyong Jin1
1a Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Science , Jilin University , Changchun 130023 , China.
Abstract:
The bacterial enzyme phosphotriesterase (PTE) exhibits stereoselectivity toward hydrolysis of chiral substrates with a preference for the Sp enantiomer. In this work, docking analysis and two explicit-solvent molecular dynamics (MD) simulations were performed to characterize and differentiate the structural dynamics of PTE bound to the Sp and Rp paraoxon derivative enantiomers (Rp-1 and Sp-1) hydrolyzed with distinct catalytic efficiencies. Comparative analysis of the molecular trajectories for PTE bound to Rp-1 and Sp-1 suggested that substrate binding induced conformational changes in the loops near the active site. After 100 ns of MD simulation, the Zn β(2+) metal ion formed hexacoordinated- and tetracoordinated geometries in the Sp-1-PTE and Rp-1-PTE ensembles, respectively. Simulation results further showed that the hydrogen bond between Asp301 and His254 occurred with a higher probability after Sp-1 binding to PTE (47.5%) than that after Rp-1 binding (22.2%). These results provide a qualitative and molecular-level explanation for the 10 orders of magnitude increase in the catalytic efficiency of PTE toward the Sp enantiomer of paraoxon.
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