Structure of 4-pyridoxolactonase fromMesorhizobium loti

Abstract

4-Pyridoxolactonase fromMesorhizobium loticatalyzes the zinc-dependent lactone-ring hydrolysis of 4-pyridoxolactone (4PAL) to 4-pyridoxic acid (4PA) in vitamin B6degradation pathway I. The crystal structures of 4-pyridoxolactonase and its complex with 5-pyridoxolactone (5PAL; the competitive inhibitor) were determined. The overall structure was an αβ/βα sandwich fold, and two zinc ions were coordinated. This strongly suggested that the enzyme belongs to subclass B3 of the class B β-lactamases. In the complex structure, the carbonyl group of 5PAL pointed away from the active site, revealing why it acts as a competitive inhibitor. Based on docking simulation with 4PAL, 4PA and a reaction intermediate, 4-pyridoxolactonase probably catalyzes the reaction through a subclass B2-like mechanism, not the subclass B3 mechanism.