Biomedical Structural Proteomics

Protein Kinase:

There are a total of about 500 distinct human kinases that can be grouped into 20 known families and an estimated 25,000 total eukaryotic kinases. Of the approximately 500 human kinase targets, only 7% are structurally represented. Interestingly, several members of the kinase family (e.g. cAMP regulated protein kinases) still have greater than 2.5 A RMSD from any other known kinase structure. We will attempt to cover 90% of the selected kinase families in the eukaryotic structural space. The protein kinase family mediates most of the signal transduction in eukaryotic cells. By modification of substrate activity, protein kinases also control many other cellular processes, including metabolism, transcription, cell cycle progression, cytoskeletal rearrangement and cell movement, apoptosis, and differentiation. Protein phosphorylation also plays a critical role in intercellular communication during development, in physiological responses and in homeostasis, and in the functioning of the nervous and immune systems. It is therefore not surprising that aberrations in protein kinases are linked to all aspects of cancer – proliferation, invasion, angiogenesis and metastasis.

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Transcription Factors:

In the human genome itself, there are an estimated 500 transcription factors and when one considers all eukaryotic transcription factors, there are more than 2000. There are approximately 160 unique structures of eukaryotic transcription factors in the PDB. The Accelerated Technologies Center for Gene to 3D Structure will attempt to complete 90% of this structural space with a fine granularity by working with 40+ eukaryotic genomes. Although a small fraction of the transcription factors selected may not be involved in cancer, by completing this structural family space, it will provide critical information towards better understanding this important protein family.

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Life Science Corridor (LSC):

The technology development and implementation program of the Accelerated Technologies Center for Gene to 3D Structure is an excellent opportunity for investigators and students from minority institutions because i) significant reduction in instrument complexity could make this type of research feasible for many institutions, ii) data generated will provide a wealth of scientific opportunities, and iii) the unique resources can be made available to external investigators. The computational implementations of the Accelerated Technologies Center for Gene to 3D Structure will allow for direct access to all experimental data during the processing as well as the consolidated views deposited with the PSI Research Network Knowledge Base. The Accelerated Technologies Center for Gene to 3D Structure has translated this opportunity by initiating a Life Sciences Corridor (LSC) Program with the University of Texas at El Paso (UTEP). The LSC will provide the general access path to the Accelerated Technologies Center for Gene to 3D Structure resources for underrepresented minority investigators and students.

The LSC will have three major elements, first at the target selection stage for which the Life Science Corridor faculty members will actively participate in this process, second an ongoing student/investigator exchange program with the goal of hosting 6 individuals per year and third an extended web-based access program for which the Accelerated Technologies Center for Gene to 3D Structure will provide access to the internal target processing and results to a group of investigators within the Corridor program. These investigators are expected to have research programs relevant to the cancer biology or other functional families within the ATCG3D targets list. The investigators and their students will then use the newly established structural information to complement other biochemical data. These investigators can request clones and expressed protein from the Accelerated Technologies Center for Gene to 3D Structure.

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