Structural and thermodynamic studies of simple aldose reductase-inhibitor complexes.

@article{Brownlee2006StructuralAT,
  title={Structural and thermodynamic studies of simple aldose reductase-inhibitor complexes.},
  author={June M. Brownlee and Erik Carlson and Amy C Milne and Erika Pape and David H. T. Harrison},
  journal={Bioorganic chemistry},
  year={2006},
  volume={34 6},
  pages={424-44}
}
The competitive inhibition constants of series of inhibitors related to phenylacetic acid against both wild-type and the doubly mutanted C298A/W219Y aldose reductase have been measured. Van't Hoff analysis shows that these acids bind with an enthalpy near -6.8 kcal/mol derived from the electrostatic interactions, while the 100-fold differences in binding affinity appear to be largely due to entropic factors that result from differences in conformational freedom in the unbound state. These… CONTINUE READING