CRYSTALLOGRAPHIC STUDIES ON HUMAN CYTOCHROME P450 3A4

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 细胞色素P450 3A 4（CYP 3A 4）是主要的zenobiotic和药物代谢酶，也参与致癌物的活化。受CYP 3A 4介导的酶促转化显著影响的领域之一是抗HIV药物的开发。迄今为止，只有有限数量的低分辨率的X射线结构的CYP 3A 4与底物，药物和抑制剂的复合物是可用的。为了更好地理解CYP 3A 4催化和抑制的机制，我们获得了与各种底物和抑制剂结合的酶的晶体，并旨在通过收集同步加速器数据来扩展其分辨率。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.