Protein X-ray Crystallographic Infrastructure for the Edinburgh Centre for Translational and Chemical Biology

爱丁堡转化和化学生物学中心的蛋白质 X 射线晶体学基础设施

• 批准号: BB/F010974/1
• 负责人: Malcolm Walkinshaw
• 金额: $ 21.05万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF010974%2F1
• 关键词: Protein; ray; Crystallographic; Infrastructure; Edinburgh

The information that is being generated from DNA sequencing is now having a major impact on the sorts of scientific questions being asked in the fields of chemistry biology and medicine. Recent examples are the discoveries linking differences in gene sequences to a number of diseases including certain types of cancers, diabetes, bipolar disorder and rheumatoid arthritis. These differences in gene sequence are translated into differences in protein structure and it is these small differences in protein structure (and therefore function) that result in differences in metabolism or signalling in the cell which are the root causes of the various disease states. Protein X-ray crystallography is a very efficient method that can be used to determine the 3D structure of these proteins and in Edinburgh there is an urgent need to upgrade our equipment to generate more results in this area. A significant amount of basic research in medicine, biology and chemistry is being driven by the new information from gene sequences. A common strand in this research is the expression and purification of the proteins derived from these key genes. At Edinburgh University we have founded a new Centre for Translational and Chemical Biology with central resources to facilitate the efficient production and purification of proteins. Over 50 independent research groups working on a wide range of medically and biologically important problems have pooled resources to speed up the process of producing and characterising proteins. Obtaining an accurate picture of the detailed structure of the protein (or protein complex) of interest provides a wealth of biologically important information that leads amongst other things, to the more efficient design of drugs. Thus, a clear picture of the molecular structure is an important research goal for every protein-based project. In order to examine the increased numbers of proteins generated at Edinburgh, we need another X-ray generator. This need is particularly urgent as one of our two generators has now failed irreparably. The data collection equipment (the image plate system, a kind of reusable X-ray photographic plate) is however still fully functioning and could be used on another X-ray source. We would like to buy a generator that can produce a more powerful beam so that we can collect better data from smaller crystals.

DNA测序产生的信息现在对化学、生物学和医学领域提出的各种科学问题产生了重大影响。最近的例子是发现基因序列的差异与一些疾病有关，包括某些类型的癌症、糖尿病、双相情感障碍和类风湿性关节炎。这些基因序列的差异转化为蛋白质结构的差异，正是这些蛋白质结构（因此功能）的微小差异导致细胞中代谢或信号传导的差异，这是各种疾病状态的根本原因。蛋白质X射线晶体学是一种非常有效的方法，可用于确定这些蛋白质的3D结构，爱丁堡迫切需要升级我们的设备，以在这一领域产生更多的结果。来自基因序列的新信息正在推动医学、生物学和化学领域的大量基础研究。本研究的一个共同点是这些关键基因衍生的蛋白质的表达和纯化。在爱丁堡大学，我们成立了一个新的转化和化学生物学中心，拥有中央资源，以促进蛋白质的有效生产和纯化。50多个独立的研究小组致力于广泛的医学和生物学重要问题，他们汇集了资源，以加快蛋白质的生产和表征过程。获得感兴趣的蛋白质（或蛋白质复合物）的详细结构的准确图片提供了大量生物学上重要的信息，这些信息尤其导致更有效的药物设计。因此，分子结构的清晰图像是每个基于蛋白质的项目的重要研究目标。为了检查爱丁堡产生的蛋白质数量的增加，我们需要另一个X射线发生器。这一需要特别紧迫，因为我们的两台发电机中有一台已经无法修复。然而，数据收集设备（图像板系统，一种可重复使用的X射线照相板）仍在充分发挥作用，可以在另一个X射线源上使用。我们想买一个能产生更强光束的发生器，这样我们就能从更小的晶体中收集更好的数据。

项目成果

`In crystallo' substrate binding triggers major domain movements and reveals magnesium as a co-activator of Trypanosoma brucei pyruvate kinase.

• DOI: 10.1107/s0907444913013875
• 发表时间: 2013-09
• 期刊: Acta crystallographica. Section D, Biological crystallography
• 作者: W. Zhong;H. P. Morgan;I. McNae;P. Michels;L. Fothergill-Gilmore;M. Walkinshaw