Quantum chemical modeling of the dehalogenation reaction of haloalcohol dehalogenase

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.