Structural adaptation of the alpha/beta hydrolase fold to an efficient decarboxylation reaction

Abstract

Numerous enzymes including lipases, esterases, and epoxide hydrolases belong to the alpha/beta hydrolase superfamily. The typical alpha/beta hydrolases catalyzing hydrolytic reactions adopt three layered-structures with a central beta-sheet flanked by alpha-helices. These enzymes have the catalytic triad composed of a nucleophilic residue, a histidine residue, and an acidic residue. The hydrogen-bonding network among the three residues in the catalytic triad plays a critical role to activate the nucelophilic residue for catalysis. In general, chemical reactions mediated by alpha/beta hydrolases are initiated by the nucleophilic residue’s attack on substrates. However, there are some alpha/beta hydrolases whose catalytic triads are used to activate H2O, HCN, H2O2, or O2 rather than the nucleophilic residue. In these enzymes, the nucleophilic attack on substrates is done by the activated H2O, HCN, H2O2, or O2. Here, we report biochemical and structural investigation of a novel alpha/beta hydrolase. According to the crystal structure, this enzyme contains no catalytic triad in spite of its canonical alpha/beta hydrolase structure, which is consistent with the biochemical observation that it has no hydrolytic activity. Instead, this enzyme harbors peculiar catalytic machinery tailored for decarboxylation reaction, which indicates that the alpha/beta hydrolase structure can be adapted to diverse reactions in addition to hydrolytic reactions.