CRYSTALLOGRAPHIC STRUCTURES OF HUMAN CYTOCHROME P450S

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cytochrome P450s catalyze the monooxygenation of wide variety of hydrophobic substrates. These enzymes are significant determinants of the bioavailability and disposition of therapeutic drugs, and better understanding of the structural determinants of substrate selectivity would facilitate the design and development of new drug candidates. We have obtained diffraction quality crystals of human liver microsomal P450 2C9dH and collected preliminary data sets to 2.4 - 2.1 ¿ resolution at SSRL Beam Line 9-1. This project is focused on data collection for a series of drug complexes of cytochrome P450 2C9, an important enzyme of human drug metabolism. These studies will provide insight into the range of structure and conformation required to explain the activity of mammalian cytochrome P450s toward an immense diversity of biological substrates and important drugs.