Ketosteroid Isomerase – Computational Studies
Synonyms
Definition
One of the most efficient enzyme catalysts known, involved in the conversion of cholesterol into testosterone.
Basic Characteristics
Ketosteroid isomerase (KSI) catalyzes the isomerization of 3-oxo-Δ5-steroids into their 3-oxo-Δ4-steroid conjugated isomers, such as 5-androstene-3,17-dione to 4-androstene-3,17-dione. The reaction starts with proton abstraction from a C-H group adjacent to a carbonyl carbon. Such carbon acid deprotonation reactions have high activation barriers in solution, but KSI catalyzes the reaction such that the enzymatic reaction rate is near the diffusion limit. Several other enzymes, such as triosephosphate isomerase and citrate synthase, catalyze similar proton abstractions from carbon atoms. There is wide interest in how these enzymes achieve efficient catalysis. In addition, KSI has been the subject of debates on the role of electrostatics in enzyme catalysis. Computer simulation of reactions has been...
References
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- Warshel A, Sharma PK, et al. Electrostatic contributions to binding of transition state analogues can be very different from the corresponding contributions to catalysis: phenolates binding to the oxyanion hole of ketosteroid isomerase. Biochemistry. 2007;46(6):1466–76.PubMedGoogle Scholar