Abstract

The focus of this proposal is to understand the basis for the specific structure/function relationship in complex protein reactions by examining differences and similarities between the 'same' protein from different organisms. This approach will help to understand the natural variation in protein structure, function and other properties between different isoforms or different species and is a necessary complement to the study of site-directed mutants of a single protein. This effort is part of a long-term interest in the use of EPR as a structural probe and draws on experience in developing and applying innovative EPR methods for answering specific biological and physical questions. This work will provide insights into the bioenergetically important cytochrome bc-type complex and the metabolically important eukaryotic cytochrome P450 enzymes that could lead to new, highly-selective drugs and antibiotics exploiting differences between these proteins in different organisms or between different isoforms in humans. The methods developed in carrying out this work will be broadly applicable to other membrane proteins and other protein complexes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM061904-04
Application #
6730528
Study Section
Metallobiochemistry Study Section (BMT)
Program Officer
Basavappa, Ravi
Project Start
2001-04-01
Project End
2006-03-31
Budget Start
2004-04-01
Budget End
2006-03-31
Support Year
4
Fiscal Year
2004
Total Cost
$315,766
Indirect Cost

  Institution

Name
Battelle Pacific Northwest Laboratories
Department
Type
DUNS #
032987476
City
Richland
State
WA
Country
United States
Zip Code
99352

  Publications

Vennam, Preethi R; Fisher, Nicholas; Krzyaniak, Matthew D et al. (2013) A caged, destabilized, free radical intermediate in the q-cycle. Chembiochem 14:1745-53
Maryasov, Alexander G; Bowman, Michael K (2013) Bloch equations for anisotropic paramagnetic centers with spin of 1/2. J Magn Reson 233:80-6
Meunier, B; Fisher, N; Ransac, S et al. (2013) Respiratory complex III dysfunction in humans and the use of yeast as a model organism to study mitochondrial myopathy and associated diseases. Biochim Biophys Acta 1827:1346-61
Bowman, Michael K; Krzyaniak, Matthew D; Cruce, Alex A et al. (2013) Skew projection of echo-detected EPR spectra for increased sensitivity and resolution. J Magn Reson 231:117-25
Maryasov, Alexander G; Bowman, Michael K (2012) Spin dynamics of paramagnetic centers with anisotropic g tensor and spin of 1/2. J Magn Reson 221:69-75
Focsan, A Ligia; Bowman, Michael K; Molnar, Peter et al. (2011) Carotenoid radical formation: dependence on conjugation length. J Phys Chem B 115:9495-506
Polyakov, Nikolay E; Focsan, A Ligia; Bowman, Michael K et al. (2010) Free radical formation in novel carotenoid metal ion complexes of astaxanthin. J Phys Chem B 114:16968-77
Roberts, Arthur G; Cheesman, Matthew J; Primak, Andrew et al. (2010) Intramolecular heme ligation of the cytochrome P450 2C9 R108H mutant demonstrates pronounced conformational flexibility of the B-C loop region: implications for substrate binding. Biochemistry 49:8700-8
Burks, Scott R; Makowsky, Mallory A; Yaffe, Zachary A et al. (2010) The effect of structure on nitroxide EPR spectral linewidth. J Org Chem 75:4737-41
Kim, Nak-Kyoon; Bowman, Michael K; DeRose, Victoria J (2010) Precise mapping of RNA tertiary structure via nanometer distance measurements with double electron-electron resonance spectroscopy. J Am Chem Soc 132:8882-4

Showing the most recent 10 out of 32 publications