Dr. Goodey’s lab conducts research in three areas that all fall under the umbrella of understanding the detailed structure and function of enzymes: Theme 1: Relationship between motion and catalysis in enzymes; Theme 2: Identification of dihydrofolate reductase enzymes from novel organisms; and Theme 3: Use of phylogenetics in predicting protein-drug interactions.
Theme 1: Relationship between motion and catalysis in enzymes
Understanding how the flexibility inherent in protein structures is related to their amazing catalytic power is a timely question that has applications in drug development and protein design. My review in 2008 in Nature Chemical Biology discusses this concept extensively. I and my students are working on understanding this important problem in two model systems: Dihydrofolate reductase from Geobacillus stearothermophilus (DHFR) and Indole-3-glycerol phosphate synthase from Sulfolobus solfataricus (IGPS). Working on one of these projects, a student will be trained in mutagenesis, protein expression and purification, attachment of probes to proteins, enzyme kinetics, ligand binding measurements and computational modeling of enzyme kinetics.
Theme 2: Identification of dihydrofolate reductase enzymes from novel organisms
I and MSU students have successfully purified and established the activity of a previously unknown dihydrofolate reductase enzyme from the fresh water snail Helisoma trivolvis. Next, we will isolate H. trivolvis mRNA and use cloning technology and degenerate primers to fish out the cDNA sequence of the gene that codes for this enzyme.
Theme 3: Use of phylogenetics in predicting protein-drug interactions
The goal of this collaborative project between me and Professor Katherine Herbert (MSU) is to establish the relationship between ligand binding and local sequence similarity in the dihydrofolate reductase enzyme family. This relationship will be used to predict the binding between existing DHFR drugs to targets in pathogenic organisms that cause tropical illnesses. I and my students will test and analyze these interactions in the laboratory.
Enzymology, enzyme kinetics, protein engineering, analyzing protein-ligand interactions