Structure-Function Relationships and Engineering of Haloalkane Dehalogenases

The structure-function relationships for haloalkane dehalogenases, one of the best characterized enzyme families involved in degradation of halogenated compounds, are described. A substantial amount of mechanistic and structural information is currently available on haloalkane dehalogenases, providing good theoretical framework for their modification by protein engineering. Examples of constructed mutants include variants with modified (i) activity and specificity, (ii) stability, and (ii) enantioselectivity. Many variants carried mutations in the tunnels connecting the buried active site with surrounding solvent, rather than in the active site itself. Mutagenesis of residues lining the protein tunnels represents attractive and a viable approach of protein engineering.