Analysis of human cytochrome P450 2C8 substrate specificity using a substrate pharmacophore and site-directed mutants.

@article{Melet2004AnalysisOH,
  title={Analysis of human cytochrome P450 2C8 substrate specificity using a substrate pharmacophore and site-directed mutants.},
  author={Armelle Melet and Cristina Marques-Soares and Guillaume A. Schoch and A C Macherey and Maryse Jaouen and Patrick M Dansette and M A Sari and Eric F Johnson and Daniel Mansuy},
  journal={Biochemistry},
  year={2004},
  volume={43 49},
  pages={15379-92}
}
The structural determinants of substrate specificity of human liver cytochrome P450 2C8 (CYP2C8) were investigated using site-directed mutants chosen on the basis of a preliminary substrate pharmacophore and a three-dimensional (3D) model. Analysis of the structural features common to CYP2C8 substrates exhibiting a micromolar K(m) led to a substrate pharmacophore in which the site of oxidation by CYP2C8 is 12.9, 8.6, 4.4, and 3.9 A from features that could establish ionic or hydrogen bonds, and… CONTINUE READING