Abstract Structure-guided rational design revealed the molecular switch manipulating the Prelog and anti-Prelog priorities of an NADPH-dependent alcohol dehydrogenase toward prochiral ketones with bulky and similar substituents. Synergistic effects of… Click to show full abstract
Abstract Structure-guided rational design revealed the molecular switch manipulating the Prelog and anti-Prelog priorities of an NADPH-dependent alcohol dehydrogenase toward prochiral ketones with bulky and similar substituents. Synergistic effects of unconserved residues at 214 and 237 in small and large substrate binding pockets were proven to be vital in governing the stereoselectivity. The ee values of E214Y/S237A and E214C/S237âŻG toward (4-chlorophenyl)-(pyridin-2-yl)-methanone were 99.3% (R) and 78.8% (S) respectively. Substrate specificity analysis revealed that similar patterns were also found with (4â-chlorophenyl)-phenylmethanone, (4â-bromophenyl)-phenylmethanone and (4â-nitrophenyl)-phenylmethanone. This study provides valuable evidence for understanding the molecular mechanism on enantioselective recognition of prochiral ketones by alcohol dehydrogenase.
               
Click one of the above tabs to view related content.