A novel pyruate decarboxylase: a cofactor-independent decarboxylation activity encoded in the α/β hydrolase structure

Abstract

Numerous enzymes including lipases, esterases, and epoxide hydrolases belong to the α/β hydrolase superfamily, the typical α/β hydrolases catalyzing hydrolytic reactions adopt three layered-structures with a central β-sheet flanked by α-helices, these enzymes have the catalytic triad composed of a nucleophilic residue, a histidine residue, and an acidic residue. The hydrogenbonding 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 α/β hydrolases are initiated by the nucleophilic residue’s attack on substrates. However, there are some α/β 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 α/β hydrolase structure, which is consistent with the biochemical observation that it has no hydrolytic activity. Instead, this enzyme harbors peculiar catalytic machinery failored for decarboxylation reaction, which indicates that the α/β hydrolase structure can be adapted to diverse reactions in addition to hydrolytic reactions.