Zhan Dongling, Guan Shanshan, Jin Hanyong, Han Weiwei, Wang Song
a Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Science , Jilin University , Changchun 130023 , China.
b College of Food Science and Engineering , Jilin Agricultural University , Changchun 130118 , China.
J Biomol Struct Dyn. 2016;34(3):600-11. doi: 10.1080/07391102.2015.1046937. Epub 2015 Jun 15.
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.
细菌酶磷酸三酯酶（PTE）对手性底物的水解表现出立体选择性，更倾向于Sp对映体。在这项工作中，进行了对接分析和两次显式溶剂分子动力学（MD）模拟，以表征和区分与具有不同催化效率水解的Sp和Rp对氧磷衍生物对映体（Rp-1和Sp-1）结合的PTE的结构动力学。对与Rp-1和Sp-1结合的PTE的分子轨迹进行比较分析表明，底物结合诱导了活性位点附近环的构象变化。经过100纳秒的MD模拟后，Zn β(2+)金属离子在Sp-1-PTE和Rp-1-PTE集合中分别形成了六配位和四配位几何结构。模拟结果进一步表明，Asp301和His254之间的氢键在Sp-1与PTE结合后出现的概率（47.5%）高于Rp-1结合后（22.2%）。这些结果为PTE对对氧磷Sp对映体催化效率提高10个数量级提供了定性和分子水平的解释。
