Faculty, Students, Alumnus Co-Author Paper in Biochemistry Journal

Wesleyan co-authors published a paper titled “The Stories Tryptophans Tell: Exploring Protein Dynamics of Heptosyltransferase I from Escherichia coli” in the January 2017 issue of Biochemistry.

The co-authors include chemistry graduate student Joy Cote; alumni Zarek Siegel ’16 and Daniel Czyzyk, PhD ’15; and faculty Erika Taylor, associate professor of chemistry; Ishita Mukerji, the Fisk Professor of Natural Science, professor of molecular biology and biochemistry.

Their paper investigates the intrinsic properties of Tryptophan amino acids found within the protein, Heptosyltransferase I, to understand the ways this protein moves during catalysis. Understanding the movement of this protein is an important step in developing its inhibitors.

When this protein is inactive, either because it was genetically altered or inhibited, hydrophobic antibiotics become more effective, so inhibitors could be useful in reactivating antibiotics that are current not effective against these bacteria.

While it is popularly believed that inhibiting a protein requires a compound to compete with the substrate, their paper argues that instead one can design a inhibitor to disrupt protein dynamics, preventing activity. The co-authors compare the function of this “protein dynamics disruptor” to a wedge holding open a door–once inserted, the inhibitor prevents the protein from performing its function.

Their research on Tryptophan residues also found that distant regions of the protein communicate whether or not they are binding their substrate to other regions.

“It would be like if your right hand knew that your left hand was holding a pencil just by the changes in the position of your left hand. We are currently pursuing computational studies to look for these motions via molecular dynamics experiments,” Taylor said.