Carnegie Mellon University

Gordon S. Rule

Professor


Address: 
246 Mellon Institute
Department of Biological Sciences
Carnegie Mellon University
4400 Fifth Avenue
Pittsburgh, PA 15213

Phone: 412-268-1839
Fax: 412-268-7129

Email

Lab website

Gordon Rule

Education

Ph.D., Carnegie Mellon University
Postdoctoral Appointment, Stanford University

Research

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, computational 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, RNA structure, 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. This is a collaborative project with Dr. Saxena at the University of Pittsburgh (Chemistry).

Protein-DNA Interactions:  In collaboration with Dr. Jen-Jacobson at the University of Pittsburgh (Biological Sciences) we are using NMR spectroscopy and thermodynamic measurements to understand the recognition of specific DNA sequences by restriction endonucleases.

Thymidylate Kinase:  We are using biophysical and computational tools to develop inhibitors of thymidylate kinases which are potential anti-bacterial, anti-fungal, and anti-malarial drugs.

Automated NMR assignments: A key bottleneck in the analysis of NMR data is the assignment of resonance lines to atoms in the protein. We are developing automated Monte-carlo methods to accomplish this task.

Publications

Lawless, M.J., Pettersson, J.P., Lanni, F., Rule, G.S., Saxena, S. (2017) ESR Shows that the C-terminus of Human Glutathione S-Transferase A1-1 Exists in Two Distinct Helical Conformations in the Ligand-Free State. Biophysical Journal, in press.

Ghosh, S., Lawless, M.J., Rule, G.S., Saxena, S. (2017) The Cu2+-nitrilotriacetic acid complex improves loading of α-helical double histidine site for precise distance measurements by pulsed ESR. J Magn Reson. 286,163-171. 

Sinha, K., Rule, G.S. (2017). The Structure of Thymidylate Kinase from Candida albicans Reveals a Unique Structural Element. Biochemistry, 56, 4360-4370.

Pettersson, J.P., Lanni, F., Rule, G.S. (2017) Dual Lifetimes for Complexes between Glutathione-S-transferase (hGSTA1-1) and Product-like Ligands Detected by Single-Molecule Fluorescence Imaging. Biochemistry. 56, 4073-4083.

Sinha, K., Sangani, S., Kehr, A., Rule, G.S., Jen-Jacobson, L. (2016) Metal ion binding at the catalytic site induces widely distributed changes in a sequence specific protein-DNA complex. Biochemistry, Biochemistry, 55, 6115-6132.

Sinha K, Jen-Jacobson L, Rule GS. Divide and conquer is always best: sensitivity of methyl correlation experiments. J Biomol NMR. 2013 Jun 15.

Sinha K, Jen-Jacobson L, Rule GS. Specific labeling of threonine methyl groups for NMR studies of protein-nucleic acid complexes. Biochemistry. 2011 Nov 29;50(47):10189-91. Epub 2011 Nov 3.

Zhan Y and Rule GS. Glutathione induces helical formation in the carboxy terminus of human glutathione transferase A1-1.Biochemistry, 43:7244-54, 2004.

Hitchens TK, Lukin JA, Zhan Y, McCallum SA and Rule GS. MONTE: An automated Monte Carlo based approach to nuclear magnetic resonance assignment of proteins. J Biomol NMR, 25:1-9, 2003.

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

Full PubMed Listings