CRYSTALLOGRAPHIC STUDIES ON HUMAN CYTOCHROME P450 3A4

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。子项目及 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 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. 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.