CRYSTALLOGRAPHIC STRUCTURES OF HUMAN CYTOCHROME P450S

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 细胞色素P450催化多种疏水底物的单氧化。这些酶是治疗药物生物利用度和处置的重要决定因素，更好地了解底物选择性的结构决定因素将有助于设计和开发新的候选药物。我们在SSRL 9-1束线上获得了人肝微粒体P450 2C9dH的衍射级晶体，并收集了分辨率为2.4-2.1？的初步数据集。本项目致力于人体药物代谢的重要酶--细胞色素P450 2C9的一系列药物络合物的数据收集。这些研究将为解释哺乳动物细胞色素P450对各种生物底物和重要药物的活性所需的结构和构象范围提供洞察力。

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.