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Structural, kinetic, and docking studies of artificial imine reductases based on biotin-streptavidin technology: An induced lock-and-key hypothesis
An artificial imine reductase results upon incorporation of a biotinylated Cp Ir moiety (Cp = C5Me5-) within homotetrameric streptavidin (Sav) (referred to as CpIr(Biot-p-L)Cl] ? Sav). Mutation of S112 reveals a marked effect of the Ir/streptavidin ratio on both the saturation kinetics as well as the enantioselectivity for the production of salsolidine. For [CpIr(Biot-p-L)Cl] ? S112A Sav, both the reaction rate and the selectivity (up to 96% ee (R)-salsolidine, kcat 14-4 min-1 vs [Ir], KM 65-370 mM) decrease upon fully saturating all biotin binding sites (the ee varying between 96% ee and 45% ee R). In contrast, for [CpIr(Biot-p-L)Cl] ? S112K Sav, both the rate and the selectivity remain nearly constant upon varying the Ir/streptavidin ratio [up to 78% ee (S)-salsolidine, kcat 2.6 min-1, KM 95 mM]. X-ray analysis complemented with docking studies highlight a marked preference of the S112A and S112K Sav mutants for the SIr and RIr enantiomeric forms of the cofactor, respectively. Combining both docking and saturation kinetic studies led to the formulation of an enantioselection mechanism relying on an “induced lock-and-key” hypothesis: the host protein dictates the configuration of the biotinylated Ir-cofactor which, in turn, by and large determines the enantioselectivity of the imine reductase.
We’ll also look at important developments in the pharmaceutical industry because understanding organic chemistry is important in understanding health, medicine, the role of 4721-98-6, and how the biochemistry of the body works.Related Products of 4721-98-6
Reference:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem