My research is directed at understanding inter-molecular interactions in biological systems. An understanding of these interactions is required if biological systems are to be comprehended at the molecular level. The combined tools of molecular biology, NMR spectroscopy and x-ray crystallography are used to provide important information to aid in our understanding of these interactions. Our research efforts have been directed at enzyme-substrate interactions, protein-lipid interactions, antibody-antigen interactions, and protein-nucleic acid interactions. Current areas of research are briefly described below.

Enzyme-Substrate Interactions: Glutathione transferases are cellular detoxification enzymes. As such, they play an important role in the protection of an organism from carcinogens and other toxic chemicals. Current efforts in my laboratory are directed at correlating substrate specificity and enzymatic mechanism with protein dynamics and substrate-protein interactions.

Protein-Nucleic Acid Interactions: We are using the RNA binding domain of E. coli Rho protein as a model of RNA-protein interactions. We are currently determining the structure of the protein and protein-nucleic acid complex by NMR and x-ray crystallography. Future studies will investigate the role of protein residues in nucleic acid binding.

Antisense RNA: In collaboration with Dr. McClure, we are investigating structural, kinetic, and dynamic aspects of important RNA-RNA interactions that occur in the pairing of ant mRNA with its antisense RNA, Sar. This interaction is important in gene regulation during the development of bacteriophage P22. The small size of these RNA molecules, the well understood kinetics of their association, and the essential role of Mg in the pairing reaction provides a unique opportunity to study RNA-RNA interactions in a well defined system. We are currently solving the structure of the individual components using multi-dimensional NMR methods on isotopically labeled material.

McCallum SA, Hitchens TK, Torborg C, Rule GS. Ligand-induced changes in the structure and dynamics of a human class Mu glutathione S-transferase. Biochemistry 2000; 39(25):7343-56. PMID: 10858281.

McCallum SA, Hitchens TK, Rule GS. Solution structure of the carboxyl terminus of a human class Mu glutathione S-transferase: NMR assignment strategies in large proteins. Journal of Molecular Biology 1999; 285(5):2119-32. PMID: 9925789.

McCallum SA, Hitchens TK, Rule GS. Unambiguous correlations of backbone amide and aliphatic gamma resonances in deuterated proteins. Journal of Magnetic Resonance 1998; 134:350-354. PMID: 9761709.

Allison TJ, Wood TC, Briercheck DM, Rastinejad F, Richardson JP, Rule GS. Crystal structure of the RNA-binding domain from transcription termination factor Rho. Nature Structural Biology 1998; 5:352-356. PMID: 9586995.

Briercheck DM, Wood TC, Allison TJ, Richardson JP,Rule GS. The NMR structure of the RNA binding domain of E. coli Rho factor suggests possible RNA-protein interactions. Nature Structural Biology 1998; 5:393-399. PMID: 9587002.