5.3 Abstract - STRUCTURAL BIOLOGY (Core Group A) The Structural Biology Shared Resource (Core Group A) brings together two major techniques for determining atomic resolution structures, Crystallography and NMR, with complementary state-of-the-art Protein Analysis technologies and expertise. These technologies have provided strong support for structural biology studies, and increasingly are also supporting drug discovery efforts by Cancer Center members. Core crystallography resources include robotics for crystallization trials and an X-ray generator with two detectors. NMR resources include four spectrometers, from a highly automated 400 MHz instrument supporting medicinal chemistry, to a 600 MHz instrument with a cryoprobe supporting structural analysis. The Protein Analysis Facility utilizes technologies including spectroscopy, analytical ultracentrifugation, and isothermal titration calorimetry, supporting the analysis of proteins, as well as protein-protein and protein-small molecule interactions. On-site custom protein production by the Facility was ended in 2013 after being found to no longer be cost-effective, but an equivalent service is available at an Institutional Core at Sanford-Burnham's Orlando, Florida site. The NMR/Crystallography and Protein Analysis Facilities are both managed by highly experienced Ph.D.-level scientists, who oversee day-to-day operations, train users, and perform or assist in experiments, as required. The services of a highly experienced crystallographer, Dr. Aleshin, were recently added to the Shared Resource, providing the final links in the pipeline from gene to protein structure that will transform the ability of scientists with little prior experience in structural biology to incorporate structural studies, as well as chemical biology, into their research programs. Dr. Aleshin manages such projects and can either provide the services or assists in handing off the project to another ?structural? collaborator. Moving forward, this service is expected to play a central role in executing our plans to incorporate structure-based drug design into the Shared Resource. While the number of direct users of the Crystallography and NMR Facility is limited, the scientific impact of such analysis is amplified through a large number of productive collaborations of these structural biologists with other Center investigators. In the past funding period, 31 Center members have received services from the Core, with more than 118 peer-reviewed papers by CC members supported by the Structural Biology Shared Resource. Of note, half of these publications utilized data from our NMR instruments. This reflects the increasing role of NMR both in chemistry including impressive work in membrane protein structure led by Dr. Marassi. A well-developed charge-back system is in place, as well as an on-line instrument-scheduling system. An advisory committee meets, as needed, to resolve any user- or management- related issues and to discuss future plans. We envisage an expanding role for the Shared Resource over the next 5 years, continuing to support outstanding basic research, and increasingly also enhancing translational aspects of Cancer Center members' science.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Center Core Grants (P30)
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Subcommittee I - Transistion to Independence (NCI)
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Sanford Burnham Prebys Medical Discovery Institute
La Jolla
United States
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