INDUCIBLE NITRIC OXIDE SYNTHASE INHIBITOR COMPLEX DATA COLLECTION

诱导型一氧化氮合酶抑制剂复合物数据收集

• 批准号: 6119464
• 负责人: Marc David Whitlow
• 金额: --
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2000-04-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6119464
• 关键词: biomaterials; enzymes; proteins

We have to collect seven high resolution data sets from flash frozen crystals of the oxygenase domain of inducible nitric oxide synthase (iNOS) inhibitor complexes at -180 C using monochromatic radiation around 1.0 E at beam line 7-1 or 9-1. Synchrotron radiation has been and still is needed due to the weak diffraction of the iNOS crystals, which only diffract to 3.5 E using a rotating anode. These structures have helped us develop selective proprietary inhibitors of human iNOS. The structural information we have gained from the high resolution structures has and will significantly enhance our ability to understand binding of these inhibitors to the iNOS and aid in the design of future iNOS inhibitors. We have been able to increase the potency of one template by 100 fold, and we now have a better understanding of the selectivity of our compounds between iNOS, nNOS and ecNOS.

我们必须从flash中收集七个高分辨率数据集 诱导型一氧化氮的加氧酶结构域的冷冻晶体 合成酶（iNOS）抑制剂复合物在-180 ℃下使用单色 在光束线7-1或9-1处的约1.0E的辐射。 同步辐射 由于iNOS的弱衍射， 晶体，其使用旋转阳极仅在3.5E下发生反应。 这些 结构帮助我们开发了选择性的专利抑制剂， 人iNOS。 我们从高海拔地区获得的结构信息 决议结构已经并将大大提高我们的能力， 为了了解这些抑制剂与iNOS的结合， 设计未来的iNOS抑制剂。 我们已经能够增加 一个模板的效力提高了100倍，我们现在有了一个更好的 了解我们的化合物在iNOS，nNOS之间的选择性 和ecNOS。