a.
Specific Aims Mitochondrial oxidative phosphorylation is a fundamental process in biological energy, transformation, and disruption of this process leads to serious human health problems, including mitochondrial myopathies, degenerative diseases, and aging. However, it has not previously been possible to measure the actual rate of electron transfer between key redox centers in this process. Millett and Durham introduced a new method to initiate electron transfer by exciting ruthenium complex with a nanosecond laser flash. This method is being used to study the pathway and kinetics of electron transfer within the cytochrome bc1 complex and cytochrome oxidase. However, the mechanism of energy coupling between cytochrome oxidase and ATP synthase is not well understood, particularly regarding the pathways of proton translocation. We propose a multi-disciplinary, collaborative approach to this problem which combines rapid kinetics techniques, bacterial model systems, and structure determination.
The specific aims will be: 1. Carry out a detailed study of electron transfer in cytochrome oxidase from Bacillus firmus that combines rapid kinetics, site-directed mutagenesis, and structure determination. Major goals will be determine the pathway and kinetics of electron transfer from cyt c through CuA and heme a to the heme a3 CuB binuclear center, as well as coupled proton uptake and release. 2. Carry out a detailed study of proton translocation and ATP synthesis in the alkaliphile B. firmus OF4 to assess the significance of alkaliphile- specific sequence motifs in the membrane-bound subunits of the Ro- ATPase. 3.Use NMR spectroscopy to study the structure of the membrane-bound subunits of the alkaliphile Fo-ATPase, primarily focusing on the isolated c subunit. Potential structural manifestations of the unusual primary amino acid sequence of the alkaliphile Fo-ATPase will be investigated.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
1P20RR015569-01
Application #
6383473
Study Section
Special Emphasis Panel (ZRR1)
Project Start
2000-09-30
Project End
2005-08-31
Budget Start
Budget End
Support Year
1
Fiscal Year
2000
Total Cost
Indirect Cost
Name
University of Arkansas at Fayetteville
Department
Type
DUNS #
191429745
City
Fayetteville
State
AR
Country
United States
Zip Code
72701
Davis, Julie Eberle; Alghanmi, Arwa; Gundampati, Ravi Kumar et al. (2018) Probing the role of proline -135 on the structure, stability, and cell proliferation activity of human acidic fibroblast growth factor. Arch Biochem Biophys 654:115-125
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