We propose to further investigate the mechanism of the bc1 complex (UQH2:cyt c2 oxidoreductase) in order to understand its role in cellular aging, and its function as the target for drugs and pest-control reagents. These latter depend on differential sensitivities to quinone-mimics that act as anti-malarial drugs, fungicides, pesti- cides, herbicides, etc., in different species. These enzymes are at the core of all major respiratory and photosynthetic pathways, and are directly responsible for about 30% of the energy conversion of the biosphere. This central importance in biology provides an intrinsic interest, relating directly to our understanding of cellular physiology, energy conversion mechanisms, and maintenance. The photosynthetic bacteria provide a model system for studying the medically important mitochondrial complex. The catalytic core of the bc1 complex is highly conserved across the mitochondrial-bacterial divide, and the reaction mechanism is essentially the same. In the bacterial system, the interplay between function and structure can be more easily studied because the system can be activated by illumination, initiating turnover in the 10

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM035438-24
Application #
8004954
Study Section
Biochemistry and Biophysics of Membranes Study Section (BBM)
Program Officer
Anderson, Vernon
Project Start
1999-01-01
Project End
2012-12-31
Budget Start
2011-01-01
Budget End
2012-12-31
Support Year
24
Fiscal Year
2011
Total Cost
$284,304
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
Barragan, Angela M; Crofts, Antony R; Schulten, Klaus et al. (2015) Identification of ubiquinol binding motifs at the Qo-site of the cytochrome bc1 complex. J Phys Chem B 119:433-47
Crofts, Antony R; Hong, Sangjin; Wilson, Charles et al. (2013) The mechanism of ubihydroquinone oxidation at the Qo-site of the cytochrome bc1 complex. Biochim Biophys Acta 1827:1362-77
Victoria, Doreen; Burton, Rodney; Crofts, Antony R (2013) Role of the -PEWY-glutamate in catalysis at the Q(o)-site of the Cyt bc(1) complex. Biochim Biophys Acta 1827:365-86
Hong, Sangjin; Victoria, Doreen; Crofts, Antony R (2012) Inter-monomer electron transfer is too slow to compete with monomeric turnover in bc(1) complex. Biochim Biophys Acta 1817:1053-62
Samoilova, Rimma I; Crofts, Antony R; Dikanov, Sergei A (2011) Reaction of superoxide radical with quinone molecules. J Phys Chem A 115:11589-93
Lhee, Sangmoon; Kolling, Derrick R J; Nair, Satish K et al. (2010) Modifications of protein environment of the [2Fe-2S] cluster of the bc1 complex: effects on the biophysical properties of the rieske iron-sulfur protein and on the kinetics of the complex. J Biol Chem 285:9233-48
Dikanov, Sergei A; Samoilova, Rimma I; Kappl, Reinhard et al. (2009) The reduced [2Fe-2S] clusters in adrenodoxin and Arthrospira platensis ferredoxin share spin density with protein nitrogens, probed using 2D ESEEM. Phys Chem Chem Phys 11:6807-19
Kolling, Derrick R J; Samoilova, Rimma I; Shubin, Alexander A et al. (2009) Proton environment of reduced Rieske iron-sulfur cluster probed by two-dimensional ESEEM spectroscopy. J Phys Chem A 113:653-67
Crofts, Antony R; Holland, J Todd; Victoria, Doreen et al. (2008) The Q-cycle reviewed: How well does a monomeric mechanism of the bc(1) complex account for the function of a dimeric complex? Biochim Biophys Acta 1777:1001-19
Rose, Stuart; Minagawa, Jun; Seufferheld, Manfredo et al. (2008) D1-arginine257 mutants (R257E, K, and Q) of Chlamydomonas reinhardtii have a lowered QB redox potential: analysis of thermoluminescence and fluorescence measurements. Photosynth Res 98:449-68

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