Seoul National
University, B.S in Agricultural Chemistry, 1985.
Korea Advanced
Institute of Science and Technology (KAIST), M. S. in Biological Science
and Technology, 1987.
University of
Nebraska-Lincoln , Ph.D. in Biochemistry, 1996.
University of California
at Irvine, Post-doctoral Associate in Molecular Biology and Biochemistry,
1996-2002.
Iron-Sulfur [Fe-S] proteins are ubiquitous occurring in all life from the most primitive bacteria and archaea to the most advanced eukaryotes. Most are intimately involved in essential electron transfer reactions in mitochondrial and other membrane-bound transport systems. Their functions, however, are not restricted to electron transfer and include chemical catalysis of hydration/dehydration reactions, regulation of gene expression, iron storage, metal cluster assembly, oxygen and iron sensing and generation and stabilization of radical intermediates. These complex and diverse chemistry of [Fe-S] clusters is employed in proteins to support many essential biological reactions (Fig. 1). In these regards, my laboratory has two primary areas of interest. One is to understand how polypeptide controls the reduction potential of [Fe-S] clusters in [Fe-S] proteins. [Fe-S] cluster by itself has an intrinsic potential based upon its chemical properties. When that [Fe-S] cluster is sitting within a protein, the surrounding protein environment will influence the reduction potential of the [Fe-S] cluster. This is one of our project; what factors of the protein structure influence the reduction potential of the [4Fe-4S] cluster in ferredoxin I (FdI)? The other area is to understand the mechanism of ability of [Fe-S] cluster to convert from one form to another. Cluster interconversion reaction is very important in vivo in several enzymes, including regulatory proteins. For example, in aconitase the 3Fe cluster is inactive, and spontaneous conversion to the 4Fe form of enzyme represents self-activation of the enzyme. For fumarate nitrate reductase (FNR), [4Fe-4S] cluster of enzyme is active and regulates a series of enzymes involved in anaerobic metabolism, but upon its conversion to [2Fe-2S] cluster in the presence of oxygen, the protein becomes inactive. Therefore, FNR regulates anaerobic metabolism by switching its [Fe-S] cluster from one type to another. Using Molecular Biology tools, we are trying to determine the protein factor to control [Fe-S] cluster interconversion in FdI.
Figure 1. Chemical structures, oxidation and spin states of 2Fe, 3Fe, and 4Fe clusters found in [Fe-S] proteins.
Aerobic organisms obtain energy by the oxidation of organic compounds using oxygen as the final electron acceptor. As a by-product of this process, reactive oxygen species generally are generated, with potentially damaging consequences for the cell. Therefore, organisms respond to the intracellular increase in reactive oxygen species by inducing sets of genes whose products either avert or repair the eventual oxidative damage. E1 subunit of pyruvate dehydrogenase complex (PDHE1) in Azotobacter vinelandii seems to respond to the intracellular increase in superoxide by inducing sets of genes whose products either avert or repair the eventual oxidative damage. In the system, 7Fe FdI appears to inhibit the transcriptional activation through fpr promoter by binding to DNA-bound PDHE1 (Fig. 2). However, little is known about how this novel system responds an intracellular increase in superoxide. For this study, we are employing proteomic techniques in conjunction with molecular biology techniques.
Figure 2.
Current working model regarding novel PDHE1/FdI Oxidative stress response
in A. vinelandii.
Chen, K., Bonagura, C.A., Tilley, G.J., McEvoy, J.P., Jung, Y.-S., Armstrong, F.A., Stout, C.D., & Burgess, B.K. (2002) Crystal structures of FdI variants exhibiting large changes in [Fe-S] reduction potential. Nature Struct. Biol. 9, 188-192.
Chen, K., Jung, Y.-S., Bonagura, C.A., Tilley, G.J., Prasad, G.S., Sridhar, V., Armstrong, F.A., Stout, C.D., & Burgess, B.K. (2002) Azotobacter vinelandii FdI: A sequence and structure comparison approach to alteration of [4Fe-4S]2+/+ reduction potential. J. Biol. Chem. 277, 5603-5610.
Jung, Y.-S., Bonagura, C.A., Tilley, G.J., Gao-Sheridan, H.S., Armstrong, F.A., Stout, C.D., & Burgess, B.K. (2000) Structure of C42D Azotobacter vinelandii FdI: A CysxxAspxxCys motif ligates an air-stable [4Fe-4S] cluster. J. Biol. Chem. 275, 36974-36983.
Jung, Y.-S., Gao-Sheridan, H.S., Christiansen, J., Dean, D.R., & Burgess, B.K. (1999) Purification and characterization of a new [2Fe-2S] Ferredoxin from Azotobacter vinelandii, a putative [Fe-S] cluster assembly/repair protein. J. Biol. Chem. 274, 32402-32410.
Lakshmi, K.V., Jung, Y.-S., Golbeck, J.H., & Brudvig, G.W. (1999) Location of the iron-sulfur clusters FA and FB in Photosystem I: An electron paramagnetic resonance study of spin relaxation enhancement of P700+. Biochemistry 38, 13210-13215.
Vassiliev, I.R., Yu, J., Jung, Y.-S., Schulz, R., Ganago, A.O., McIntosh, L., & Golbeck, J.H. (1999) The cysteine-proximal aspartates in the FX-binding niche of Photosystem I: Effect of alanine and lysine replacements on photoautotrophic growth, electron transfer rates, single-turnover flash efficiency, and EPR spectral properties. J. Biol. Chem. 274, 9993-10001.
Jung, Y.-S., Roberts, V.A., Stout, C.D., and Burgess, B.K. (1999) Complex formation between Azotobacter vinelandii Ferredoxin I and its physiological electron donor NADPH-Ferredoxin Reductase. J. Biol. Chem. 274, 2978-298.
Phone: (662) 325-2763
Fax: (662) 325-8664
Internet:
yj29@Ra.MsState.edu
