Ground state destabilization from a positioned general base in the ketosteroid isomerase active site.

@article{Ruben2013GroundSD,
  title={Ground state destabilization from a positioned general base in the ketosteroid isomerase active site.},
  author={Eliza A Ruben and Jason P Schwans and Matthew Sonnett and Aditya Natarajan and Ana Carolina Gonzalez and Yingssu Tsai and Daniel Herschlag},
  journal={Biochemistry},
  year={2013},
  volume={52 6},
  pages={1074-81}
}
We compared the binding affinities of ground state analogues for bacterial ketosteroid isomerase (KSI) with a wild-type anionic Asp general base and with uncharged Asn and Ala in the general base position to provide a measure of potential ground state destabilization that could arise from the close juxtaposition of the anionic Asp and hydrophobic steroid in the reaction's Michaelis complex. The analogue binding affinity increased ~1 order of magnitude for the Asp38Asn mutation and ~2 orders of… CONTINUE READING