X-RAY CRYSTALLOGRAPHY OF ENZYMES INVOLVED IN DRUG METABOLISM, BACTERIAL INFECTIO

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的研究机构。 Redinbo小组使用结构，分子和化学生物学的工具来研究动态细胞和系统过程。 我们专注于四个中心领域：1）转录控制和治疗开发中的核受体，2）化学疗法和化学保护中的酶，3）DNA操纵机械结构，功能和抑制，以及4）细菌发病机制。 这些领域重叠，例如，我们研究DNA松弛酶和解旋酶，催化细菌抗生素抗性基因在细菌细胞之间的转移;从而影响区域3和4。 我们研究了核受体PXR如何与人体外来的异生物质化学物质结合，并促进其失活，包括抗癌药物，从而影响区域1和2。 我们的主要目标有两个：推进结构生物学的使用，以告知新的治疗方法如何针对细菌感染，并帮助设计策略，以增加有用的治疗化合物在人体内的寿命。 我们在本提案中针对的结构将对这些目标产生重大影响。

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. The Redinbo group uses the tools of structural, molecular and chemical biology to examine dynamic cellular and systemic processes. We focus on four central areas: 1) Nuclear Receptors in transcriptional control and therapeutic development, 2) enzymes in chemotherapy and chemoprotection, 3) DNA manipulation machinery structure, function and inhibition, and 4) Bacterial pathogenesis. These areas overlap, for example we study DNA relaxases and helicases that catalyze the transfer of bacterial antibiotic resistance genes between bacterial cells; thus impacting area 3 & 4. We study how the nuclear receptor PXR binds to xenobiotic chemicals that are foreign to the human body and promotes their inactivation, including anticancer drugs, thus impacting areas 1 & 2. Our main goals are twofold: to advance the use of structural biology to inform how new therapeutics can be directed against bacterial infection, and to help design strategies to increase the lifetime of useful therapeutic compounds in the human body. The structures we target in this proposal will significantly impact these goals.