Enzymes use protein architectures to create highly specialized structural motifs that can greatly enhance the rates of complex chemical transformations. In this talk I will discuss our recent research using experiments, combined with ab initio simulations that exactly include nuclear quantum effects, which show that a triad of strongly hydrogen-bonded tyrosine residues within the active site of the enzyme ketosteroid isomerase (KSI) facilitate quantum proton delocalization. This delocalization dramatically stabilizes the deprotonation of an active-site tyrosine residue, resulting in a very large isotope effect on its acidity. When an intermediate analog is docked, it is incorporated into the hydrogen-bond network, giving rise to extended quantum proton delocalization in the active site. These results shed light on the role of nuclear quantum effects in the hydrogen-bond network that stabilizes the reactive intermediate of KSI, and the behavior of protons in biological systems containing strong hydrogen bonds.

Nuclear and electronic delocalization in enzyme hydrogen bond networks

251st National Meeting (2016)

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