Summery: Discovered nearly 70 years ago, the enzyme E. coli aspartate transcarbamoylase (ATCase) is discussed in every biochemistry textbook. ATCase catalyzes a key step in the metabolic pathway that produces pyrimidine nucleotides, and it has long been known that the final products of this pathway inhibit the enzyme by inducing so-called cooperative behavior. But what does it mean for the active sites of an enzyme to "cooperate"? And how do small molecules like nucleotides interact with the enzyme to tune this property? Despite decades of research on this famous enzyme, the molecular basis of its nucleotide-based regulation surprisingly remained elusive. In this talk, I will cover the historical context of this mystery and how our understanding of ATCase was shaped by the birth and growth of structural biology. I will then discuss how we used small-angle X-ray scattering, cryo-electron microscopy, X-ray crystallography, and biochemical assays. Our results indicate that nature has evolved a remarkably elegant mechanism, where the structural dynamics of ATCase are controlled by the balance of complementary sets of nucleotides in the cell. This, in turn, controls how much the active sites of the enzyme must work together to achieve chemistry.

Profile: Dr. Nozomi Ando is an associate professor at Chemistry and Chemical Biology in Cornell University.
Nozomi Ando | Department of Chemistry and Chemical Biology