Ketosteroid isomerase reaction

KSI has been used as a model system to test different theories to explain how enzymes achieve their catalytic efficiency. Low-barrier hydrogen bonds and unusual pKa values for the catalytic residues have been proposed as the basis for the fast action of KSI. [10] [15] Gerlt and Gassman proposed the formation of unusually short, strong hydrogen bonds between KSI oxanion hole and the reaction intermediate as a means of catalytic rate enhancement. [34] [35] In their model, high-energy states along the reaction coordinate are specifically stabilized by the formation of these bonds. Since then, the catalytic role of short, strong hydrogen bonds has been debated. [36] [37] Another proposal explaining enzyme catalysis tested through KSI is the geometrical complementarity of the active site to the transition state, which proposes the active site electrostatics is complementary to the substrate transition state . [8]

Ketosteroid isomerase has become a test enzyme in the debate over the existence of low barrier hydrogen bonds (LBHBs) in accordance with the hydrogen bonding discussed above. Nuclear magnetic resonance (NMR) studies of KSI in complex with transition state analogs have revealed the presence of a highly shielded proton characteristic of the formation of a LBHB between Tyr 14 and the O-3 atom of the analogs and suggestive of the formation of a bridging hydrogen with short bonds. [3] , [17] , [7] Additionally, NMR fractionation studies with deuterium substitution are strongly suggestive of the high strength of this bond as deuterium is retained preferentially in this position. [17] The energy of this bond along with that of the normal hydrogen bond from Asp 99 most likely contribute to the energy needed to support proton abstraction from the C-4 position. [3]

Ketosteroid isomerase reaction

ketosteroid isomerase reaction


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