A computational study of the dechlorination of β-hexachlorocyclohexane (β-HCH) catalyzed by the haloalkane dehalogenase LinB.
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 β-hexachlorocyclohexane (β-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 SN2 dechlorination reaction between β-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 β-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 β-HCH to the active site of LinB has been compared to the binding of smaller 1-chlorobutane (1-CB) and larger δ-hexabromocyclododecane (δ-HBCD).
['Manna|Rabindra Nath|RN|', 'Dybala-Defratyka|Agnieszka|A|']
D001426:Bacterial Proteins D002073:Butanes D002384:Catalysis D020134:Catalytic Domain D002712:Chlorides D002713:Chlorine D019295:Computational Biology D001556:Hexachlorocyclohexane D006842:Hydrocarbons, Brominated D006860:Hydrogen Bonding D006867:Hydrolases D056004:Molecular Dynamics Simulation D011485:Protein Binding D020578:Sphingomonas D013379:Substrate Specificity D013499:Surface Properties
Dechlorination β-HCH LinB QM/MM DFT MD