Bacterial 2-haloacid dehalogenases: Structures and catalytic properties

2-Haloacid dehalogenases (2-haloacid halidohydrolase; EC class: 3.8.1.2) catalyze the hydrolytic dehalogenation of 2-haloalkanoic acids to produce the corresponding 2-hydroxyalkanoic acids. Four different groups of 2-haloacid dehalogenases have been found in bacterial cells. The carboxylate group of Asp(10) of L-2-haloacid dehalogenase acts as a nucleophile on the alpha-carbon of L-2-haloalkanoic acid to form an ester intermediate, which is hydrolyzed to produce the corresponding 2-hydroxyalkanoic acid. In contrast, in the reaction of DL-2-haloacid dehalogenase (inversion type), a water molecule activated by the enzyme directly attacks the alpha-carbon of the substrate. D-2-Haloacid dehalogenase shows sequence similarity to DL-2-haloacid dehalogenase (inversion type), suggesting that the reaction mechanism of D-2-haloacid dehalogenase is similar to that of DL-2-haloacid dehalogenase (inversion type). Only the DL-2-haloacid dehalogenase (retention type) reaction proceeds with retention of the C-2-configuration of the substrate, and its reaction mechanism is probably different from those of other 2-haloacid dehalogenases.