Hydrogen bonding in the active site of ketosteroid isomerase: electronic inductive effects and hydrogen bond coupling.

ABSTRACT: Computational studies are performed to analyze the physical properties of hydrogen bonds donated by Tyr16 and Asp103 to a series of substituted phenolate inhibitors bound in the active site of ketosteroid isomerase (KSI). As the solution pK(a) of the phenolate increases, these hydrogen bond distances decrease, the associated nuclear magnetic resonance (NMR) chemical shifts increase, and the fraction of protonated inhibitor increases, in agreement with prior experiments. The quantum mechanical/molecular mechanical calculations provide insight into the electronic inductive effects along the hydrogen bonding network that includes Tyr16, Tyr57, and Tyr32, as well as insight into hydrogen bond coupling in the active site. The calculations predict that the most-downfield NMR chemical shift obser

SUBMITTER: Hanoian P 

PROVIDER: S-EPMC2996240 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature