CRYSTALLOGRAPHIC STRUCTURES OF HUMAN CYTOCHROME P450S

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 细胞色素P450催化多种疏水底物的单加氧。 这些酶是治疗药物的生物利用度和处置的重要决定因素，并且更好地理解底物选择性的结构决定因素将促进新候选药物的设计和开发。 我们已经获得了人肝微粒体P450 2C 9dH的衍射质量晶体，并在SSRL光束线9-1收集了2.4 - 2.1分辨率的初步数据集。 本项目主要研究人体药物代谢的重要酶细胞色素P450 2C 9的一系列药物复合物的数据收集。 这些研究将提供深入了解所需的结构和构象的范围来解释哺乳动物细胞色素P450对生物底物和重要药物的巨大多样性的活性。

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.