Structure and dynamics of nucleic acids; human hemoglobin: structure and function; NMR spectroscopy.
Our research program is focused on understanding the relationship between structure and function in biological macromolecules using nuclear magnetic resonance (NMR) spectroscopy and other biophysical techniques.
One project in the laboratory centers on the structure and dynamics of nucleic acids. DNA and RNA molecules of unique base sequences (for example, tracts of AT base pairs, repeats of the CA/GT motif and base-pair mismatches) are being synthesized and labeled with 15N, 13C and 2H at specific sites using chemical or enzymatic methods. Depending on the base sequence, these molecules can assume a variety of conformations: double helix, bent double helix, hairpin, bulge or triple helix. The detailed structure of each is determined directly in solution by multi-dimensional NMR methods such as those illustrated in the figure: nuclear Overhauser enhancement spectroscopy (NOESY) and double-quantum filtered correlation spectroscopy (DQF-COSY). Hydrogen exchange and NMR relaxation measuremens are also being used to map the internal dynamics of individual bases and of specific functional sites in the nucleic acid molecules of interest.
A second project in the laboratory aims at understanding the molecular mechanisms responsible for the cooperative binding of oxygen to human hemoglobin and for the allosteric effects of other components of the red blood cells upon hemoglobin function. The human hemoglobin used in our studies is obtained by expressing the corresponding globin genes in E.Coli. Using NMR spectroscopy we are investigating the factors that influence the structural integrity of this recombinant hemoglobin. Our goal is to identify the conditions under which this recombinant hemoglobin can be used as a blood substitute.
- Folta-Stogniew and I. M. Russu, “Sequence Dependence of Base-Pair Opening in a DNA Dodecamer Containing the CACA/GTGT Sequence Motif.,” Biochemistry, 33:11016 (1994).
- J. G. Moe, E. Folta-Stogniew, and I. M. Russu, “Energetics of Base-Pair Opening in a DNA Dodecamer Containing an A3T3 Tract,” Nucleic Acids Research, 23:1984 (1995).
- E. Folta-Stogniew, and I. M. Russu, “Base-Catalysis of Imino Proton Exchange in DNA: Effects of Catalyst upon DNA Structure and Dynamics,” Biochemistry ,35:8439 (1996).
- R. Michalczyk, L. A. Silks, and I. M. Russu, “1H and 15N NMR Investigation of a DNA Dodecamer Containing an A3T3 Tract,” Magnetic Resonance in Chemistry, 34:S97 (1996).
- I. M. Russu., “Protein Structure Determination by Nuclear Magnetic Resonance Spectroscopy, in Advances in Molecular and Cell Biology: Protein Structure and Folding,” JAI Press ,(1997).
- M. T. Sanna, A. Razynska, M. Karavitis, A. P. Koley, F. K. Friedman, I.M. Russu, W. S. Brinigar, and C. Fronticelli, “Assembly of Human Hemoglobin: Studies with Escherichia Coli Expressed α-Globin,” Journal of Biological Chemistry, 272:3478 (1997).
- R. Michalczyk, and I. M. Russu, “Studies of the dynamics of adenine amino protons by 15N labeling and heteronuclear NMR spectroscopy,” Proceedings of the Tenth Conversation. Albany, N.Y. (1998).
- R. Michalczyk, and I. M. Russu, “Rotational Dynamics of Adenine Amino Groups in a DNA Double Helix,” Biophysical Journal, 76:2679 (1999).
- M.-R. Mihailescu, and I. M. Russu, “A signature of the T-> R transition in human hemoglobin,” Proceedings of the National Academy of Sciences U.S.A. ,98:3773 (2001).
- M.-R. Mihailescu, C. Fronticelli, and I. M. Russu, “Allosteric Free Energy Changes at the α1β2 Interface of Human Hemoglobin Probed by Proton Exchange of Trpβ37,” PROTEINS: Structure, Function, and Genetics, 44:73 (2001).
- L. Jiang, and I. M. Russu, “Proton exchange and local stability in a DNA triple helix containing a G.TA triad,” Nucleic Acids Research, 29:4231 (2001).
- S. W. Powell, L. Jiang, and I. M. Russu, “Proton Exchange and Base-Pair Opening in a DNA Triple Helix,” Biochemistry, 40:11065 (2001).
- D. Coman, and I. M. Russu, “Site-Resolved Energetics in DNA Triple Helices Containing G.TA and T.CG Triads,” Biochemistry, 41:4407 (2002).
- L. Jiang, and I. M. Russu, “Internal Dynamics in a DNA Triple Helix Probed by 1H-15N NMR Spectroscopy,” Biophysical Journal, 82:3181 (2002).
- I. N. Rujan, and I. M. Russu, “Allosteric Effects of Chloride Ions at the α1ß1and α2ß2 Interfaces of Human Hemoglobin,” PROTEINS: Structure, Function and Genetics, 49:413 (2002)
- D. Coman, and I. M. Russu, “Probing Hydrogen Bonding in a DNA Triple Helix Using Protium-Deuterium Fractionation Factors,” Journal of the American Chemical Society, 125:6626 (2003).
- I. M. Russu, “Probing Site-Specific Energetics in Proteins and Nucleic Acids by Hydrogen Exchange and NMR Spectroscopy,” Methods in Enzymology, 379:152 (2004).
- D. Coman, and I. M. Russu, “Site-Resolved Stabilization a DNA Triple Helix by Magnesium Ions,” Nucleic Acids Research, 32:878 (2004).
- C. Chen, and I. M. Russu, “Sequence-Dependence of the Energetics of Opening of AT Base Pairs in DNA,” Biophysical Journal , 87:2545 (2004).
- D. Coman, and I. M. Russu, “Base-Pair Opening in Three DNA Unwinding Elements,” Journal of Biological Chemistry, 280:20216 (2005).
- D. Coman, and I. M. Russu, “A Nuclear Magnetic Resonance Investigation of the Energetics of Basepair Opening Pathways in DNA,” Biophysical Journal ,89:3285 (2005).
- C. Chen, L. Jiang, R. Michalczyk, and I. M. Russu, “Structural Energetics and Base-Pair Opening Dynamics in Sarcin-Ricin Domain RNA, ” Biochemistry, 45:13606 (2006).
- A. E. Every, and I. M. Russu, “Probing the Role of Hydrogen Bonds in the Stability of Base Pairs in Double-Helical DNA,” Biopolymers, 87:165 (2007).
- A. E. Every, and I. M. Russu, “Influence of Magnesium Ions on Spontaneous Opening of DNA Base Pairs,” Journal of Physical Chemistry, B 112:7689 (2008).
- Y. Huang, C. Chen and M. Russu, “Dynamics and Stability of Individual Base Pairs in Two Homologous RNA-DNA Hybrids, Biochemistry, 48, 3988-3997 (2009).
B.S. 1968 University of Bucharest, Romania, Physics
Ph.D. 1979 University of Pittsburgh, Biophysics