Structural Biology Shared Service

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6.0 Abstract: Structural Biology Shared Service The Structural Biology Shared Service (SBSS) provides investigators with the facilities and expertise to collect and interpret molecular structural information (nuclear magnetic resonance [NMR], X-ray crystallography) to understand the molecular mechanism(s) of action of proteins and enzymes that contribute to cancer. The SBSS also facilitates identification of molecular agents (e.g., candidate drugs, molecular probes) that can be used to study the function of cancer targets and may have therapeutic potential. To achieve this mission, the SBSS implements a structural biology approach. This includes isolation and characterization of samples for NMR and X ray and application of state-of-the-art data collection methods in a collaborative environment that facilitates access by UMGCC investigators. In 2014, 36 UMGCC investigators used the SBSS. These investigators deposited 84 high-resolution structures into the protein database in addition to publishing in high- impact journals. The efforts of the SBSS have facilitated development of several novel, cancer target–specific small-molecule inhibitors. Interactions between the SBSS and investigators from multiple UMGCC programs have facilitated the integration of structural biology into the translational research efforts of UMGCC. Also of significance, the SBSS installed and commissioned a new 950 MHz NMR spectrometer purchased through an $8 million NIH Shared Instrumentation Grant. This is the only such instrument available in an academic institution in the United States and represents the largest Shared Instrumentation Grant awarded by NIH. The SBSS has also expanded and upgraded X-ray diffraction and robotic crystallization resources to enhance the use of these resources. In 2014, the SBSS supported 36 Cancer Center members spanning all 5 research programs (14 percent of all UMGCC members); 53 percent of UMGCC users have peer-reviewed funding. The SBSS supports many cancer-related publications annually, many in high-impact journals including Proceedings of the National Academy of Sciences of the United States of America, Journal of Medicinal Chemistry, and Nature Structural & Molecular Biology.