CRYSTAL STRUCTURE DETERMINATION OF H PYLORI VACA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 幽门螺杆菌是一种定植于人类胃部的细菌。这种细菌及其产生的VacA蛋白毒素对胃癌的发展至关重要，胃癌是全球与癌症相关的死亡的第二大原因，也是消化性溃疡疾病的第二大原因。我们建议测定VacA的三维结构，以期了解这种毒素--S的作用机制。我们在内部获得了衍射率为2.0°的Vaca晶体。VacA是新的，因为它与其他已知的蛋白质没有序列同源性。我们计划用MAD方法对这种结构进行定相，因此获得波长可调的同步加速器光束线是必不可少的。我们已经制备了硒蛋氨酸、铂和汞衍生晶体，为这些同步加速器MAD实验做准备。我们还预计，同步加速器光束线提供的准直良好的光束和更大的探测器将帮助我们解析260°单元格边缘的斑点。

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. Helicobacter pylori is a bacterium that colonizes the human stomach. The bacterium, along with the VacA protein toxin it produces, is important in the development of gastric cancer, the second leading cause of cancer-related death worldwide, and in peptic ulcer disease. We propose to determine the three-dimensional structure of VacA in an effort to understand this toxin?s mechanism of action. We have obtained crystals of VacA that diffract to 2.0 ¿ in-house. VacA is novel in that it does not share sequence homology with other known proteins. We plan to phase this structure by MAD methods and therefore access to a synchrotron beamline with tunable wavelengths is essential. We have prepared selenomethionine, platinum, and mercury derivitized crystals in preparation for these synchrotron MAD experiments. We also anticipate that the well-collimated beam and larger detectors offered at synchrotron beamlines will help us resolve spots from our 260 ¿ cell edge.