Biophysical Chemistry

My research interests are focused generally on the functional energetics of regulatory proteins. My laboratory uses a range of genetic and biophysical methods to yield structural, kinetic and energetic clues towards elucidating the rules governing molecular control mechanisms in proteins. Two systems are currently being investigated.

Regulation of catalysis in allosteric threonine deaminase

Allosteric enzymes play a pivotal role in cellular regulation by controlling the conversion of substrates to products early in a metabolic pathway. Our efforts on this problem are directed towards forging a quantitative mechanism for the regulation of substrate binding and catalysis by a family of pyridoxal phosphate dependent threonine deaminases. Our approach consists of analyzing complementary information from structural, genetic, thermodynamic and kinetic studies to yield more accurate insights into the fundamental interactions between subunits that give rise to cooperative ligand binding and the feedback regulation of substrate binding and catalysis in threonine deaminase by isoleucine and valine.

Control of cellular protein folding by GroEL/GroES chaperones.

Although many proteins spontaneously adopt a unique three-dimensional structure, the heat shock proteins GroES and GroEL from Escherichia coli have been shown to facilitate the ATP-dependent hydrolysis-dependent acquisition of native structure of proteins from unfolded chains. Our approach is to evaluate the energetics and kinetics of the interactions of GroEL with nonnative polypeptides, nucleotides and the co-chaperonin GroES to elucidate the elementary steps in a single cycle of chaperonin function.