"Allostery in a Radical Enzyme"
|Date/Time:||Monday, 04 Feb 2013 from 3:10 pm to 4:00 pm|
The balance of ribonucleotides and deoxyribonucleotides is critical for genetic stability and is thus exquisitely maintained in the cell. The enzyme, ribonucleotide reductase (RNR), lies at the heart of this process. RNRs are responsible for all de novo biosynthesis of DNA precursors in nature by catalyzing the conversion of ribonucleotides into deoxyribonucleotides. Using sophisticated allostery, RNRs also control the intracellular balance of nucleotides. However, the molecular basis of this regulation had been enigmatic for nearly half a century, largely due to a lack of structural information on how the subunits interact. Using four techniques (small-angle X-ray scattering, X-ray crystallography, electron microscopy, and analytical ultracentrifugation), we demonstrate that the prototypic RNR from Escherichia coli exists as a mixture of species whose distributions are modulated by allosteric effectors. We further show that the interconversion between active and inactive forms entails dramatic subunit rearrangements, providing a stunning molecular explanation for the allosteric regulation of RNR activity in E. coli.
Biography: Nozomi Ando received her Ph.D. in physics from Cornell University and B.S. in physics from MIT. She performed her dissertation research in the group of Prof. Sol Gruner (Cornell Physics) on protein folding thermodynamics as a function of pressure. Nozomi is currently an NIH Pathway to Independence postdoctoral fellow in the group of Prof. Catherine Drennan (MIT Chemistry), where she has been studying metalloenzymes with importance to medicine, climate, and energy.