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中文摘要
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描述(由申请者提供):一个新的X光设备将使NIH赞助的19项赠款的全部潜力得以实现。现有的X射线发生器已有22年的历史,不再起作用;现有的区域探测器和低温设备已有10年的历史,维护起来不再具有成本效益。所要求的设备是:Rigaku MSC,Inc.,MicroMAX-002密封管微焦点X射线源,配备高性能共焦最大通量光学元件,产生单色、聚焦的X射线束,其通量是现有RU200旋转阳极发电机的3倍;土星944CCDX射线面积探测器,活动图像面积为94 mm x 94 mm,可提供8兆赫读数、15100:1动态范围和高灵敏度;AFC-11计算机控制的四轴测角仪;以及X-STREAM-2000型低温系统。该设备将为生物大分子的所有结晶学实验提供高通量仪器能力,包括筛选晶体质量和膜蛋白质和蛋白质-DNA复合体的低温保护条件,以及从数百个蛋白质晶体收集高分辨率数据。可靠的内部X射线设备将加速许多晶体的预筛选,优化膜蛋白质的同步辐射时间的使用,并为药物开发和蛋白质工程实验实现结构测定。还要求升级专门设计的单晶显微分光光度计,用于在探索机理的实验中评估蛋白质氧化状态和活性中心化学。显微分光光度计对于将生化性质与晶体结构相关联是必不可少的,并将直接与新的X射线设备一起使用。新设备将使所有七个主要调查人员的项目受益,他们在合作和共享使用现有X射线设备方面有着长期和富有成效的记录。这种新设备的维护成本低,而且是在美国制造的。新的X射线设施将为结晶学方法的研究生和博士后研究员提供实践培训机会,并将促进科学互动,提高学习和研究的质量,并有助于在学术和生物医学部门保留和创造就业机会。新设备是一项长期投资,因为现有的X射线发生器已经使用了20多年,现有的探测器和低温设备已经使用了10年。 与健康相关:结晶学实验需要可靠的内部X射线设备,以高通量筛选晶体质量和低温保护条件,并从数百种蛋白质晶体中收集高分辨率数据。需要新设备来支持这些实验,以支持由七名主要调查人员指导的19项NIH现行拨款。
英文摘要
DESCRIPTION (provided by applicant): A new X-ray facility will enable the full potential of 19 NIH sponsored grants to be realized. An existing X-ray generator is 22 years old and no longer functional; the existing area detector and low temperature device is 10 years old and no longer cost-effective to maintain. The equipment requested is: a Rigaku MSC, Inc., MicroMax-002+ sealed tube microfocus X-ray source coupled with a high performance Confocal Max-Flux optic that produces a monochromatic, focused X-ray beam with flux 3X greater than the existing RU200 rotating anode generator; a Saturn 944+ CCD X-ray area detector with 94 mm x 94 mm active image area that provides 8 MHz readout, 15100:1 dynamic range, and high sensitivity; a AFC-11 computer controlled 4-axis goniometer; and a X-STREAM-2000 low temperature system. This equipment will provide high throughput instrumental capacity for all crystallographic experiments with biological macromolecules, including screening for crystal quality and cryoprotection conditions with membrane proteins and protein-DNA complexes, and high resolution data collection from many hundreds of protein crystals. A reliable, in-house X-ray facility will accelerate prescreening of many crystals, optimize the use of synchrotron beam time for membrane proteins, and enable structure determination for drug discovery and protein engineering experiments. Equipment items are also requested to upgrade a specially designed single crystal microspectrophotometer for evaluation of protein oxidation states and active site chemistry in experiments that probe mechanism. The microspectrophotometer is essential to correlate biochemical properties with crystal structures, and will be used in direct conjunction with the new X-ray facility. The new equipment will benefit the projects of all seven principle investigators, who have a long and productive track record of collaboration and shared use of the existing X-ray equipment. The new equipment is cost-effective to maintain, and is manufactured in the United States. The new X-ray facility will provide hands-on training opportunities for graduate students and postdoctoral fellows in crystallographic methods, and will stimulate scientific interactions, enhance the quality of learning and research, and help to retain and create jobs in the academic and biomedical sectors. The new equipment is a long term investment, given that the existing X-ray generator was in use over 20 years, and the existing detector and low temperature device have been in use for 10 years. HEALTH RELEVANCE: Crystallographic experiments require a reliable in-house X-ray facility for high throughput screening of crystal quality and cryoprotection conditions, and for high resolution data collection from many hundreds of protein crystals. The new equipment is required to support these experiments for 19 active NIH grants being directed by seven principle investigators.
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Transhydrogenase: Structure, Dynamics, and Mechanism
  • 批准号:
    8853878
  • 项目类别:
  • 资助金额:
    $36.01万
  • 财政年份:
    2014
  • 负责人:
    Charles David Stout
  • 依托单位:
Transhydrogenase: Structure, Dynamics, and Mechanism
  • 批准号:
    8629282
  • 项目类别:
  • 资助金额:
    $36.01万
  • 财政年份:
    2014
  • 负责人:
    Charles David Stout
  • 依托单位:
STRUCTURAL GENOMICS OF CYTOCHROME P450S
  • 批准号:
    8362153
  • 项目类别:
  • 资助金额:
    $0.41万
  • 财政年份:
    2011
  • 负责人:
    Charles David Stout
  • 依托单位:
FRAGMENT BASED DRUG DISCOVERY TARGETING HIV PROTEASE
  • 批准号:
    8362285
  • 项目类别:
  • 资助金额:
    $2.71万
  • 财政年份:
    2011
  • 负责人:
    Charles David Stout
  • 依托单位:
海外基金