This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The rise in obesity in the United States parallels a dramatic increase in obesity-associated diseases, most notably type-2 diabetes. This disease is predicted to reach epidemic proportions in the next several decades. A drug of choice to treat type-II diabetes is pioglitazone, a thiazolidinedione (TZD) derivative originally thought to exert its effect through activation of the nuclear transcription factor PPAR. Recently, the structure of a novel protein target, mitoNEET, was determined to 1.5 ? resolution using data collected from BL9-2 [Paddock, M. L., Wiley, S. E., Axelrod, H. L., Cohen, A. E., Roy, M., Abresch, E. C., Capraro, D., Murphy, A. N., Nechushtai, R., Dixon, J. E. and Jennings, P. A. Proc. Natl. Acad. Sci. USA 104, 14342 (2007)]. MitoNEET is a particularly interesting target for structure-based drug design as it binds insulin-sensitizing drugs and it possesses a novel molecular structure which includes an unusually labile iron-sulfur cluster. Structural studies of MitoNEET were continued this year with the goals of studying the structure with the drug pioglitazone bound and to observe structural changes at lower pH, and of crystals of the soluble domain of the human mitoNEET protein.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
2P41RR001209-31
Application #
8170076
Study Section
Special Emphasis Panel (ZRG1-BCMB-P (40))
Project Start
2010-05-01
Project End
2011-02-28
Budget Start
2010-05-01
Budget End
2011-02-28
Support Year
31
Fiscal Year
2010
Total Cost
$1,349
Indirect Cost
Name
Stanford University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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