Figure 4

Stereospecific binding for the asymmetric reduction of 3-quinuclidinone by RrQR. A 3-quinuclidinone in the active site of RrQR is shown by a stick model and in cyan. a The catalytic model of 3-quinuclidinone-RrQR ensures the product (R)-3-quinuclidinol. The hydrophobic wall comprised of I167 and F212 is adjacent to the hydrophobic side of the substrate, which stabilizes the substrate binding. The tertiary amine group of the substrate is exposed to solvent. b The noncatalytic model of 3-quinuclidinone-RrQR leads to the product (S)-3-quinuclidinol. The hydrophobic wall is adjacent to the amine group of the substrate, resulting in an unstable state. A hydrophobic surface of the substrate is exposed to solvent. c The refined structure of RrQR by an energy minimization (red) is superimposed on the structure of the catalytic model shown in Figure 4a (blue). d Schematic diagram of the catalytic mechanism of RrQR. The hydride transfer from NADPH to the carbonyl carbon of 3-quinuclidinone is depicted by an arrow. The hydrophobic wall comprised of I167 and F212 is adjacent to the hydrophobic surface of the substrate. The hydrogen bonds in the active site are shown by dotted lines. The hydroxyl group of the product is shown in red.