Experimental and computational investigations of the haloalkane dehalogenases and their interactions with ionic liquids

A. Shaposhnikova1, T. Prudnikova1,2, B. Minofar2, I. Kuta Smatanova1,2

1Faculty of Science, University of South Bohemia in Ceske Budejovice, Czech Republic
2Institute of Microbiology of the Czech Academy of Sciences, Nove Hrady, Czech Republic

Haloalkane dehalogenases (HLDs) are microbial enzymes that catalyze the cleavage of a carbon-halogen bond by a hydrolytic mechanism. The reaction products are halide ion, hydronium ion (proton) and an alcohol molecule. These enzymes can be useful for the biodegradation of many important environmental pollutants such as 1,2-dichloroethane, 1,2,3,4,5,6-hexachlorocyclohexane, and 1-chlorobutane [1].

The haloalkane dehalogenase DhaA from Rhodococcus rhodochrous is a monomeric enzyme with molecular weight of 34 kDa and it is a representative of the large superfamily of α/βhydrolases [1]. Mutant variant DhaA80 with enhanced structural and kinetic stability in the presence of dimethyl sulfoxide and the elevated temperature was constructed by directed evolution and site-directed mutagenesis. The crystallization experiment was performed using the sitting-drop vapor-diffusion method at a temperature of 4°C. Crystals of DhaA80 grown from the precipitant containing 20% PEG 3350, 0.2M sodium fluoride and ionic liquids (IL) from Hampton Research Ionic Liquid Screen - HR2-214. Crystals diffracted to the resolution of 1.8Å. The known structure of HLD from Rhodococcus sp. (www.rcsb.org) was used as a template for molecular replacement. The structures of DhaA80 including IL solutions containing 1) 50% w/v 2-Hydroxyethylammonium formate, 2) 50% w/v 1-Butyl-3-methylimidazolium dicyanamide and 3) 50% w/v 1-Butyl-3-methylimidazolium methyl sulfate were solved after several refinements and validations. For further research and understanding, the interaction of ILs ions molecular dynamics (MD) simulations have been used. MD simulations of systems containing DhaA80 with 50% w/v 1-Butyl-3-methylimidazolium methyl sulfate and 50% w/v 2-Hydroxyethylammonium formate have been performed. The analysis of MD data by using root mean square deviation (RMSD) and root mean square fluctuations (RMSF) confirmed that ILs affect the structure and stability of enzyme.

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