Random microseeding as a new approach applied on haloalkane dehalogenase DbeA variant crystallisation

Tatyana Prudnikova1,2, Ekaterina Sviridova1,2, Pavlina Rezacova3, Radka Chaloupkova4, Yukari Sato5, Michal Kuty1,2, Tana Koudelakova4, Yuji Nagata5, Jiri Damborsky4, and Ivana Kuta Smatanova1,2

1Faculty of Science, University of South Bohemia Ceske Budejovice, Branisovska 1760, 370 05 Ceske Budejovice, Czech Republic

2Institute of Nanobiology and Structural Biology, Institute of Microbiology, Academy of Sciences of the Czech Republic, Zamek 136, 373 33 Nove Hrady, Czech Republic

3Institute of Organic Chemistry and Biochemistry and Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Flemingovo n.2, Prague 6, Czech Republic

4 Loschmidt Laboratories, Department of Experimental Biology and Research Centre for Toxic Compounds in the Environment, Faculty of Science, Masaryk University, Kamenice 5/A4, 625 00 Brno, Czech Republic

5 Department of Environmental Life Sciences, Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Sendai 980-8577, Japan

 

A novel enzyme, DbeA, belonging to the family of haloalkane dehalogenases (EC 3.8.1.5) was isolated from Bradyrhizobium elkanii USDA94. This haloalkane dehalogenase is closely related to DbjA enzyme from Bradyrhizobium japonicum USDA110 (71% sequence identity), but has different biochemical properties. DbeA is generally less active and has a higher specificity towards brominated and iodinated compounds than DbjA. The DbeA protein was crystallised using the sitting-drop vapour-diffusion method and the crystal structure of a DbeA enzyme has been solved and deposited at Worldwide Protein Data Bank under PDB ID 4k2a. The DbeA wt structure revealed the presence of two halide-binding sites. The first chloride-binding site is located in the active site in between two halide-stabilizing residues. The second chloride-binding site is unique to DbeA and has not been previously reported in any other structure of this enzyme family. To elucidate the role of the second halide-binding site, a two-point variant DbeA ΔCl (I44L+Q102H) lacking this site was constructed and biochemically characterized [1]. Elimination of the second halide-binding site decreased the stability and catalytic activity, and dramatically altered the substrate specificity. The two-point substitution resulted in a shift of the substrate-specificity class, which is the first time this has been demonstrated for this enzyme family. Rational design of buried halide-binding sites represents a novel strategy for engineering of enzymes with modified catalytic properties.

1.         Chaloupkova R, et al., Acta Crystallogr. D70, 1884-1897 (2014)