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.

Public 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.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Biomedical Research Support Shared Instrumentation Grants (S10)
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Special Emphasis Panel (ZRG1-BCMB-D (30))
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Levy, Abraham
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Scripps Research Institute
La Jolla
United States
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