Fig. 7: Modeling of key variants M1, M3, and M6.
From: Effective engineering of a ketoreductase for the biocatalytic synthesis of an ipatasertib precursor
Homology models of wild-type Ssal-KRED (light gray) and variants M1 (smudge), M3 (wheat) and M6 (slate) with binding modes of 1a. The cofactor is shown in pale yellow, sand, yellow and orange, respectively. Catalytic residues are indicated in red letters. a Superimposed WT and M1 displaying the aromatic cage-like binding site formed by F97W, M242W and W226 in the latter (only one variant is shown for clarity). b Close-up view on key positions 241, 242 and 245 in the WT, M3 and M6. Coordination of 1a by catalytic S133 and Y177 is indicated in blue and red dashes for the WT and M6, respectively. c Polar interactions of key position 134 with other residues in the WT (blue dashes) and M6 (red dashes). Interactions with P206 and N207 are lost in variant M6. d Secondary structure differences on positions 97, 238 and 241 between WT and all evolved variants. Mutation A238K in M3 and M6 might act as a “tunnel gate” residue.
