Dr. Betty Jean Gaffney
Personal Home Page
Professor, Florida State University, 1996-present
B.S. 1961 (Chemistry), Stanford
Ph.D. 1966 (Chemistry), Stanford
NIH Postdoctoral Fellowship 1966, Tohoku University, Sendai Japan
Varian Assoc. Postdoctoral Fellowship 1967
Research Associate, Stanford 1968-1973
NIH Research Career Development Award, 1975-80
Assistant Professor to Professor, Johns Hopkins University, 1974-1996.
Fellow of the Biophysical Society, 2009.
Graduate Faculty Status
Research and Professional Interests:
Lipids mediators; lipoxygenase enzymes; magnetic resonance spectroscopy.
Lipoxygenases are a large family of enzymes important in development and inflammation. The problem that has fascinated investigators for many years, including researchers in my lab, is that lipoxygenase protein structures are highly conserved from bacteria to eukaryotes, yet, how different family members target oxygen stereospecifically to carbons 5, 8, 9, 11, 12 or 15 on arachidonic acid remains poorly understood. The site of arachidonate oxidation is specific to the pathway that will subsequently be activated in cells. These pathways include inflammatory and anti-inflammatory ones, and lipid remodeling in development. Our specialty involves using electron paramagnetic resonance (EPR) spectroscopy for unique approaches to understanding the mechanism of lipoxygenases. Over the years, we have developed computer programs to help us understand how iron participates in lipoxygenase mechanisms and, in a collaboration, how manganese can be an unusual substitute for iron. We also collaborate on selected X-ray crystal structures of lipoxygenases. Most recently, we returned to an early interest of mine, paramagnetic probes (spin labels) of protein structure. Using spin labels, we show where a substrate enters a lipoxygenase active site, a subject that has been elusive in studies of crystals.Selected Publications:
Bowers, C. R., V. Storhaug, C. E. Webster, J. Bharatam, A. Cottone III, R. Gianna, K. Betsey, and B.J. Gaffney (1999). Exploring protein surfaces and cavities in lipoxygenase and other proteins by hyperpolarized xenon-129 NMR. Journal of the American Chemical Society 121: 9370-9377. PMID: 16429610. Full text, PDF
Coffa, G., A. N. Imber, B. C. Maguire, G. Laxmikanthan, C. Schneider, B. J. Gaffney, and A. R. Brash. 2005. On the relationships of substrate orientation, hydrogen abstraction and product stereochemistry in single and double dioxygenations by soybean lipoxygenase-1 and its Ala542Gly mutant. Journal of Biological Chemistry 280: 38756-38766. PMID: 16157595. Full text, PDF
Youn, B. Y., G. E. Sellhorn, R. J. Mirchel, B. J. Gaffney, H. D. Grimes, and C. H. Kang. 2006. Crystal structures of vegetative soybean lipoxygenase VLX-B and VLX-D, and comparisons with seed isoforms, LOX-1 and LOX-3. PROTEINS: Structure, Function, and Bioinformatics 65: 1008-1020. PMID: 17022084.
Wu, F. Y., and B. J. Gaffney. 2006. Dynamic behavior of fatty acid spin labels within a binding site of soybean Lipoxygenase-1. Biochemistry 45:12510-12518. PMID: 17029406.
Gaffney, B. J. 2009. EPR of mononuclear iron proteins. Pages 233-268 in Biological Magnetic Resonance, Vol 28. High Resolution EPR: Applications to Metalloenzymes and Metals in Medicine, G. Hanson and L. J. Berliner, eds. Springer Verlag. ISBN 978-0-64655-6. Full text, PDF. See Figure 9 in color.
Gaffney, B. J., M. D. Bradshaw, S. Frausto, F. Wu, J. H. Freed, and P. Borbat. 2012. Locating a lipid at the portal to the lipoxygenase active site. Biophysical Journal 103:2134-2144. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3512035. See also Supplemental information.
Gaffney, B.J. (2014) “Connecting Lipoxygenase Function to Structure by Electron Paramagnetic Resonance” Accounts of Chemical Research 47: 3588-3595. http://dx.doi.org/10.1021/ar500290r.