Hopmann Kathrin H, Himo Fahmi
Department of Theoretical Chemistry, School of Biotechnology, Royal Institute of Technology, AlbaNova University Center, SE-106 91 Stockholm, Sweden.
J Chem Theory Comput. 2008 Jul;4(7):1129-37. doi: 10.1021/ct8000443.
The dehalogenation reaction of haloalcohol dehalogenase HheC from Agrobacterium radiobacter AD1 was investigated theoretically using hybrid density functional theory methods. HheC catalyzes the enantioselective conversion of halohydrins into their corresponding epoxides. The reaction is proposed to be mediated by a catalytic Ser132-Tyr145-Arg149 triad, and a distinct halide binding site is suggested to facilitate halide displacement by stabilizing the free ion. We investigated the HheC-mediated dehalogenation of (R)-2-chloro-1-phenylethanol using three quantum chemical models of various sizes. The calculated barriers and reaction energies give support to the suggested reaction mechanism. The dehalogenation occurs in a single concerted step, in which Tyr145 abstracts a proton from the halohydrin substrate and the substrate oxyanion displaces the chloride ion, forming the epoxide. Characterization of the involved stationary points is provided. Furthermore, by using three different models of the halide binding site, we are able to assess the adopted modeling methodology.
利用杂化密度泛函理论方法对根癌土壤杆菌AD1的卤代醇脱卤酶HheC的脱卤反应进行了理论研究。HheC催化卤代醇对映选择性转化为相应的环氧化物。该反应被认为是由催化性的Ser132-Tyr145-Arg149三联体介导的，并且有人提出一个独特的卤化物结合位点通过稳定自由离子来促进卤化物的取代。我们使用三种不同大小的量子化学模型研究了HheC介导的(R)-2-氯-1-苯乙醇的脱卤反应。计算得到的势垒和反应能量支持了所提出的反应机理。脱卤反应以单一协同步骤发生，其中Tyr145从卤代醇底物中夺取一个质子，底物氧负离子取代氯离子，形成环氧化物。提供了所涉及驻点的表征。此外，通过使用卤化物结合位点的三种不同模型，我们能够评估所采用的建模方法。
