This application proposes to establish an Oklahoma Center of Biomedical Research Excellence (COBRE) in Structural Biology. Structural biology is a multidisciplinary research area that focuses on the important relationship between macromolecular structure and function. A structural biology approach can be taken to study any area of biological science and thus it has had a major impact on both basic and applied biomedical research. At the OU-Norman and OUHSC campuses, a number of research groups utilize a structural approach to study important biological macromolecules, in particular, proteins or nucleic acids that are promising targets for rationale drug design. Because of the multidisciplinary nature of structural biology, the training of students, postdocs, and researchers new to the field can be challenging. In addition, the instrumentation required for structural biology is both expensive and sophisticated. The overall objective of this proposal is to establish an Oklahoma COBRE in Structural Biology in order to build and nurture a critical mass of researchers in this area and support their research programs through shared resources and expertise.
The specific aims of this application are to: 1) Further the research activities and career development of junior investigators through senior mentorship and strengthening of research infrastructure;2) Create state-wide core facilities in macromolecular X-ray crystallography, high throughput crystallization, and protein expression/purification, which will provide users access to shared major instrumentation, staff support and research training;and 3) Promote structural biology in the State of Oklahoma through COBRE activities such as annual symposia, workshops, a seed grant program and core research facilities. Collectively, these specific aims are expected to increase the pace, competitiveness and success rate of structural biology research groups in Oklahoma as they seek major independent external grant support.
Structural biology lies at the intersection of many different areas of biological sciences and thus has the potential of impacting numerous biomedically important fields. The specific research projects proposed herein have direct relevance to human diseases and conditions associated with aging, osteoporosis, diabetes, bacterial and parasitic infections.
|Hanigan, Marie H; Gillies, Elizabeth M; Wickham, Stephanie et al. (2015) Immunolabeling of gamma-glutamyl transferase 5 in normal human tissues reveals that expression and localization differ from gamma-glutamyl transferase 1. Histochem Cell Biol 143:505-15|
|Hanigan, Marie H (2014) Gamma-glutamyl transpeptidase: redox regulation and drug resistance. Adv Cancer Res 122:103-41|
|West, Matthew B; Chen, Yunyu; Wickham, Stephanie et al. (2014) Novel insights into eukaryotic ýý-glutamyltranspeptidase 1 from the crystal structure of the glutamate-bound human enzyme. J Biol Chem 289:11569|
|Ding, Jingzhen; Mooers, Blaine H M; Zhang, Zhi et al. (2014) After embedding in membranes antiapoptotic Bcl-XL protein binds both Bcl-2 homology region 3 and helix 1 of proapoptotic Bax protein to inhibit apoptotic mitochondrial permeabilization. J Biol Chem 289:11873-96|
|Sheikh, M Osman; Schafer, Christopher M; Powell, John T et al. (2014) Glycosylation of Skp1 affects its conformation and promotes binding to a model f-box protein. Biochemistry 53:1657-69|
|West, Matthew B; Chen, Yunyu; Wickham, Stephanie et al. (2013) Novel insights into eukaryotic ýý-glutamyltranspeptidase 1 from the crystal structure of the glutamate-bound human enzyme. J Biol Chem 288:31902-13|
|Wickham, Stephanie; Regan, Nicholas; West, Matthew B et al. (2013) Inhibition of human ýý-glutamyl transpeptidase: development of more potent, physiologically relevant, uncompetitive inhibitors. Biochem J 450:547-57|
|Isom, Catherine E; Turner, Jessica L; Lessner, Daniel J et al. (2013) Redox-sensitive DNA binding by homodimeric Methanosarcina acetivorans MsvR is modulated by cysteine residues. BMC Microbiol 13:163|
|Thomas, Leonard M; Harper, Angelica R; Miner, Whitney A et al. (2013) Structure of Escherichia coli AdhP (ethanol-inducible dehydrogenase) with bound NAD. Acta Crystallogr Sect F Struct Biol Cryst Commun 69:730-2|
|Hill, Heather E; Pioszak, Augen A (2013) Bacterial expression and purification of a heterodimeric adrenomedullin receptor extracellular domain complex using DsbC-assisted disulfide shuffling. Protein Expr Purif 88:107-13|