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. Multidrug resistance is a serious medical problem and presents a major challenge to the treatment of disease and the development of novel therapeutics. ABC transporters that are associated with multidrug resistance move hydrophobic drugs and lipids from the inner to the outer leaflet of the cell membrane. E.coli MsbA lipopolysaccharide (lipid A) flippase is homolog of mammalian P-glycoproteins. Different transporters are thought to have a common mechanism based on ATP binding and hydrolysis to energize the substrate translocation. The structure of MsbA in vesicles is different from that in detergent used in X-ray crystallography. Therefore, the study of MsbA conformational changes produced by ATP hydrolysis in the lipid environment is valuable, but requires methods suited for such case. Distance constraints from ESR are well up to the task. We plan to determine a critical set of such constraints to undersand better the MsbA conformational changes.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR016292-09
Application #
7956624
Study Section
Special Emphasis Panel (ZRG1-BCMB-K (40))
Project Start
2009-09-01
Project End
2010-08-31
Budget Start
2009-09-01
Budget End
2010-08-31
Support Year
9
Fiscal Year
2009
Total Cost
$2,226
Indirect Cost
Name
Cornell University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Jain, Rinku; Vanamee, Eva S; Dzikovski, Boris G et al. (2014) An iron-sulfur cluster in the polymerase domain of yeast DNA polymerase ?. J Mol Biol 426:301-8
Pratt, Ashley J; Shin, David S; Merz, Gregory E et al. (2014) Aggregation propensities of superoxide dismutase G93 hotspot mutants mirror ALS clinical phenotypes. Proc Natl Acad Sci U S A 111:E4568-76
Georgieva, Elka R; Borbat, Peter P; Ginter, Christopher et al. (2013) Conformational ensemble of the sodium-coupled aspartate transporter. Nat Struct Mol Biol 20:215-21
Airola, Michael V; Sukomon, Nattakan; Samanta, Dipanjan et al. (2013) HAMP domain conformers that propagate opposite signals in bacterial chemoreceptors. PLoS Biol 11:e1001479
Airola, Michael V; Huh, Doowon; Sukomon, Nattakan et al. (2013) Architecture of the soluble receptor Aer2 indicates an in-line mechanism for PAS and HAMP domain signaling. J Mol Biol 425:886-901
Sun, Yan; Zhang, Ziwei; Grigoryants, Vladimir M et al. (2012) The internal dynamics of mini c TAR DNA probed by electron paramagnetic resonance of nitroxide spin-labels at the lower stem, the loop, and the bulge. Biochemistry 51:8530-41
Smith, Andrew K; Freed, Jack H (2012) Dynamics and ordering of lipid spin-labels along the coexistence curve of two membrane phases: an ESR study. Chem Phys Lipids 165:348-61
Yu, Renyuan Pony; Darmon, Jonathan M; Hoyt, Jordan M et al. (2012) High-Activity Iron Catalysts for the Hydrogenation of Hindered, Unfunctionalized Alkenes. ACS Catal 2:1760-1764
Gaffney, Betty J; Bradshaw, Miles D; Frausto, Stephen D et al. (2012) Locating a lipid at the portal to the lipoxygenase active site. Biophys J 103:2134-44
Dzikovski, Boris; Tipikin, Dmitriy; Freed, Jack (2012) Conformational distributions and hydrogen bonding in gel and frozen lipid bilayers: a high frequency spin-label ESR study. J Phys Chem B 116:6694-706

Showing the most recent 10 out of 72 publications