   1.1.1.358 | (R)-pantolactone + NADP+ = 2-dehydropantolactone + NADPH + H+ |
catalytic mechanism of (R)-pantolactone synthesis, overview. The conserved catalytic triad is formed by residues Thr30, Tyr66 and His128. Tyr66 functions as a proton donor following hydrogen transfer from NADPH. Thr30 and His128 are critical residues to bind and orient 2-dehydropantolactone (KPL). The phenolic hydroxyl group of Tyr66 forms the hydrogen bond with the C5 carbonyl oxygen of 2-dehydropantolactone. The HR of NADPH could just attack the si-face of the carbonyl group, which results in the formation of (R)-pantolactone. The alpha-amino group and the hydroxyl group of Thr30 form hydrogen bonds with the C4 carbonyl oxygen of KPL, and the epsilon-amino group of Lys33 formes the hydrogen bond with the O2 of KPL. In addition, the hydrophobic interaction of His128, Val165 and Phe302 with two methyl groups of KPL might facilitate the substrate binding |
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