The X-ray crystallography facility at Pennsylvania State University desperately needs to upgrade the aged Rigaku macromolecular crystallography instrument and the outdated Bruker small molecule X-ray diffractometer with a reconfiguration of the two available ports on the Rigaku MicroMax007 X-ray generator. The improvements we wish to have on the right port are ?Varimax-VHFarc)sec? optics with higher flux suitable for small sized crystals of around 40?m, a typical size in our crystallization trials; a universal four-circle kappa goniometer for efficient data collection; and a shutter-less, large area, highly sensitive HyPix-Arc 150 detector to detect weak diffraction from macromolecular crystals. We also wish to upgrade to an oxford cryo-stream for cooling the crystals during data collection. For the left port we wish to configure it for small angle X-ray scattering (SAXS) with the BioSAXS- 2000 2D-Kratky system. This upgrade will enable both small and macromolecular X-ray crystallography on the right port and add a new capability, solution SAXS on the left port. SAXS technique has the advantage of determining a low-resolution structure with a fast turnaround time and not having to grow crystals. We have identified the Rigaku components as the sole commercial product which meets our requirements, is state-of-the- art and cost-effective. Having a higher X-ray flux and improved sensitivity is paramount for the success and throughput of all the cutting-edge X-ray crystallography projects described in this proposal. The controlling and analyzing software for both crystallography and SAXS provided by Rigaku is user friendly and loaded with features for data processing and analysis. Upgrading the X-ray equipment is a desperate need to the success of the twenty active NIH structural biology projects and two pending NIH grants participating in this shared instrumentation proposal. This will enhance all the forefront research projects listed in the summary tables (a) small molecule drug development research in Sharma and Giri labs (b) structure-function of proteins and their complexes with nucleic acids in Murakami, Tan and Krasilnikov labs (c) enable a unique anaerobic SAXS tool for the metallobiochemistry group including Booker, Boal and Bollinger labs working with oxygen sensitive proteins and (d) facilitate rapid access to in-house SAXS equipment for the RNA samples that are prone to misfolding/aggregation being studied in the Bevilacqua, Showalter, Krasilnikov labs. With the upgraded single crystal and SAXS ports we would be investing in true synergy where-in the whole becomes greater than the sum of the parts. Experimental results from crystallography would guide the interpretation of SAXS and low-resolution solvent envelope models as obtained from SAXS of protein-protein or protein - nucleic acid or nucleic acid multimers could help in the crystallographic study of these complexes at higher resolution.

Public Health Relevance

We seek funds to upgrade the components on our existing MicroMax 007 X-ray generator and reconfigure its two ports at the established and productive X-ray crystallography facility at Pennsylvania State University. For the right port we need Varimax-VHFarc)sec optics, a universal four-circle kappa goniometer, a HyPix-Arc 150 detector and an oxford cryo-stream to enable small and macromolecular crystallography; and on the left port we need the BioSAXS-2000 2D- Kratky system to study solution small angle X-ray scattering. The ten NIH funded faculty who have participated in the current proposal as major users and the twenty-two NIH projects that they work on would benefit tremendously by this upgrade.

National Institute of Health (NIH)
Office of The Director, National Institutes of Health (OD)
Biomedical Research Support Shared Instrumentation Grants (S10)
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Special Emphasis Panel (ZRG1)
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Wang, Guanghu
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Pennsylvania State University
Schools of Arts and Sciences
University Park
United States
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