A computational study of the dechlorination of beta-hexachlorocyclohexane (beta-HCH) catalyzed by the haloalkane dehalogenase LinB

作者：Manna Rabindra Nath; Dybala Defratyka Agnieszka^*

来源：Archives of Biochemistry and Biophysics, 2014, 562: 43-50.

DOI：10.1016/j.abb.2014.07.028

• LinB
• beta-HCH
• Dechlorination
• DFT
• QM/MM
• MD

LinB, a haloalkane dehalogenase from Sphingomonas paucimobilis UT26, is known to metabolize halohydrocarbons to halide ions and the respective alcohols. Its broad substrate specificity allowed its consideration for bioremediation. Herein, we have shown its catalytic action toward beta-hexachlorocyclohexane (beta-HCH) - an example of large-size substrates that can be accommodated in its active site. We have analyzed the capability of combined QM/MM schemes to describe in detail the S(N)2 dechlorination reaction between beta-HCH and Asp108 in the active site of LinB. Free energy surfaces have been calculated using one and two dimensional potentials of mean force (PMF) obtained at the PM3/MM (MM = amberff99SB, TIP3P) level of theory. The overestimated energetic barriers by the PM3 Hamiltonian were corrected using a DFT functional (M06-2X). The resulted activation energies (16 and 19 kcal mol(-1) from 1D and 2D-PMF profiles, respectively) for the dechlorination reaction of beta-HCH in the active site of LinB enzyme are in qualitative agreement with the experimentally determined value of 17 kcal mol(-1). The binding of beta-HCH to the active site of LinB has been compared to the binding of smaller 1-chlorobutane (1-CB) and larger delta-hexabromocyclododecane (delta-HBCD).

• 出版日期2014-11-15