CRYSTALLOGRAPHIC STUDIES ON HUMAN CYTOCHROME P450 3A4

人细胞色素 P450 3A4 的晶体学研究

• 批准号: 8170293
• 负责人: IRINA F SEVRIOUKOVA
• 金额: $ 0.03万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170293
• 关键词: Affect; Anti-HIV Agents; Area; Binding; Carcinogens; Catalysis; Complex; Computer Retrieval of Information on Scientific Projects Database; Cytochrome P450; Cytochrome P450 3A4; Data; Development; Enzymes; Funding; Grant; Human; Institution; Mediating; Pharmaceutical Preparations; Research; Research Personnel; Resolution; Resources; Source; Structure; Synchrotrons; United States National Institutes of Health; inhibitor/antagonist

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 P450 3A4 (CYP3A4) is the major zenobiotic- and drug-metabolizing human enzyme that is also involved in carcinogen activation. One of the areas significantly affected by the CYP3A4-mediated enzymatic transformations is development of anti-HIV drugs. To date, only a limited number of low-resolution x-ray structures of CYP3A4 complexes with substrates, drugs and inhibitors are available. To better understand the mechanism of CYP3A4 catalysis and inhibition, we obtained crystals of the enzyme bound to various substrates and inhibitors and aim to extend their resolution by collecting synchrotron data.

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 3A4(CYP3A4)是人类主要的生态酶和药物代谢酶，也参与了致癌物的激活。受CYP3A4介导的酶转化显著影响的领域之一是抗HIV药物的开发。到目前为止，只有有限数量的低分辨X射线结构的CYP3A4与底物，药物和抑制剂的络合物是可用的。为了更好地了解CYP3A4的催化和抑制机制，我们获得了该酶与各种底物和抑制剂结合的晶体，目的是通过收集同步加速器数据来扩大它们的分辨率。