Biomolecular Sciences Seminar Series

Dr. Martin St. Maurice, Marquette University

Title: A Swing and a Miss: Allostery and Carrier Domain Dynamics in Pyruvate Carboxylase

Abstract: To achieve catalysis, the biotinylated carrier domain of pyruvate carboxylase undergoes a large-scale domain movement of more than 60 angstroms as it transitions between two remotely located active sites. We have used structural, biochemical and biophysical methods to probe the range of carrier domain movement in this enzyme and to examine the factors contributing to carrier domain positioning. This work demonstrates that carrier domain positioning is governed by conformational selection that is sensitive to the presence of substrates and allosteric effectors.  These allosteric effectors, both activators and inhibitors, bind at an allosteric “hot spot” at the dimer interface between two domains.  We are seeking to better define this binding site to gain better insights into the molecular basis for allosteric regulation in this enzyme and to exploit as a possible target for pharmacological effectors.

Host: Dr. Rajesh Nagarajan