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中文摘要
翻译
该子项目是利用 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来源获得主要资金, 因此可以在其他CRISP条目中表示。列出的机构是 中心,不一定是研究者的机构。 提出了一系列人类和细菌蛋白质的晶体学研究,统一的主题是每种蛋白质在人类疾病中发挥作用。 首先,假单胞菌蛋白PilY 1的结构将使用MAD和SAD方法的组合进行研究。 这种蛋白质是将感染性假单胞菌附着到肺上皮的粘附物,导致囊性纤维化(CF)患者的致命定植。 第二,将在与神经毒剂的复合物中确定人类药物代谢蛋白羧酸酯酶1(hCE 1)的晶体结构(例如,沙林、梭曼)和神经毒剂类似物。 第三,将确定人类核受体的晶体结构。 例如,核异生素受体PXR的结构将在与各种药物和拮抗剂的复合物中确定; PXR是人类的中心药物受体,并控制肝脏和其他组织中主要药物代谢途径的表达。在hCE 1和核受体的情况下,需要同步辐射,因为我们所研究的晶体
英文摘要
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. Crystallographic studies of a series of human and bacterial proteins are proposed, with the unifying theme that each protein plays a role in human disease. First, the structure of the Pseudomonas protein PilY1 will be pursued using a combination of MAD and SAD methodologies. This protein is the adhesion that attaches the infectious Psuedomonas bacterium to the lung epithelia, leading to lethal colonizations in patients with cystic fibrosis (CF). Second, crystal structures of the human drug metabolism protein carboxylesterase 1 (hCE1) will be determined in complexes with nerve agents (e.g., sarin, soman) and nerve agent analogues. Third, crystal structures of human nuclear receptors will be determined. For example, structures of the nuclear xenobiotic receptor PXR will be determined in complexes with various drugs and antagonists; PXR is the central drug receptor in humans and controls the expression of the primary drug metabolism pathways in liver and other tissues. In the cases of hCE1 and nuclear receptors, synchrotron radiation is required because the crystals we have diffract to
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Understanding and Controlling Drug Metabolism by the Gut Microbiota to Improve Human Health
Understanding and Controlling Drug Metabolism by the Gut Microbiota to Improve Human Health
Structural Basis for Hormone and Neurotransmitter Processing by Gut Microbial Enzymes
Structural Basis for Hormone and Neurotransmitter Processing by Gut Microbial Enzymes
国内基金
海外基金
Segmented Filamentous Bacteria激活宿主免疫系统抑制其拮抗菌 Enterobacteriaceae维持菌群平衡及其机制研究
  • 批准号:
    81971557
  • 项目类别:
    面上项目
  • 资助金额:
    65.0万元
  • 批准年份:
    2019
  • 负责人:
    毛开睿
  • 依托单位:
电缆细菌(Cable bacteria)对水体沉积物有机污染的响应与调控机制