The mission of the Macromolecular Structure and Interactions Shared Resource (MSISR) is to provide CTRC members with state-of-the-art resources for investigating molecular mechanisms by which macromolecules function and for discovering novel targeted cancer therapies. The MSISR has three components: X-ray crystallography (X-ray), Nuclear Magnetic Resonance (NMR), and Macromolecular Interactions (MMI). The MSISR has supported mechanistic studies of cancer-related macromolecules since 2003. Recent emphasis has been on translating basic knowledge into discovering and developing small molecules for probing biological mechanisms related to cancer, and possibly for treating cancer. X-ray laboratory instrumentation includes a crystallization robot, an automated crystal imaging system, and two X-ray data collection systems for obtaining high quality 3-D structures of proteins, nucleic acids and their complexes. The NMR component includes spectrometers with high sensitivity cryoprobes and automatic sample changers operating at 500, 600, and 700 MHz, for obtaining 3-D solution structures and investigating interactions with other macromolecules and potential therapeutic agents. The MMI component includes surface plasmon resonance (SPR), analytical ultracentrifugafion (AUC), dynamic and static light scattering (DLS and SLS), and isothermal titration calorimetry (ITC) instrumentation, providing a complementary set of tools for characterizing the kinetics, thermodynamics and stoichiometry of binding. The MSISR also has a 2,000 compound fragment library and liquid handler to prepare protein samples for screening using NMR, SPR, and X-ray. The MSISR is staffed by PhD technical managers ( X-ray and NMR) and a full-time MS-trained technical manager (MMI) who provide guidance at each step. The X-ray and MMI are located on the Long Campus, while the NMR is located on the Greehey Campus. Overall scientific oversight is provided by Dr. Andrew Hinck, while oversight of the components is provided by faculty with expertise in these areas (Dr. Hinck - NMR, Dr. P. John Hart - X-ray, Dr. Eileen Lafer - MMI). The MSISR is jointly managed by the CTRC and the UTHSCSA,. The MSISR was utilized in the past award year by 25 CTRC members.
The CTRC MSISR provides an array of technologies that allows CTRC investigators to understand how cancer-related macromolecules function at the molecular level. The MSISR also provides capabilities discovering and developing small molecules that target cancer-related macromolecules, allowing CTRC investigators to investigate novel targeted therapies for cancer treatment and to probe biological mechanisms and pathways related to cancer.
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