Computer-Assisted, Structure-Based Prediction of Substrates for Cytochrome P450_(cam)

摘要

Cytochrome P450 enzymes catalyze an impressive array of oxidative transformations, but the factors that determine their substrate specificities are poorly understood. The ability to predict whether a molecule would be a substrate from knowledge of the active site structure and an understanding of the factors that determine substrate specificity are critical if new activities and specificities are to be engineered into P450 enzymes by mutagenesis. In addition, elucidation of the factors that determine substrate specificity is required to understand, predict, and attempt to modulate the physiological metabolism of Pharmaceuticals and other xenobiotics. We report here successful use of a computer-based docking program to predict whether compounds entirely unrelated to camphor are substrates for Cytochrome P450_(cam), a protein that normally oxidizes camphor and for which a crystal structure is available.