Biological Chemistry Seminar Speaker: Dr. Nozomi Ando

Dec 6, 2023 at - | Carolyn Hoff Lynch Lecture Hall

Conformational Switching in a Dynamic Vitamin B12 Enzyme

Flexible, multi-domain enzymes catalyze remarkable chemical transformations by moving either their co-factor or substrate over large distances, from active site to active site. A classic example is the cobalamin-dependent methionine synthase (MetH), which performs three different reactions by moving its cobalamin (vitamin B12) cofactor between three different active sites. Decades of biochemical and structural work on this enzyme have shown that it has a flexible “beads on a string” topology that adopts two major conformations. However, it had never been visualized in its entirety. In this talk, I’ll describe how we combined small-angle X-ray scattering, cryo-electron microscopy, and large-scale analysis of AlphaFold2 predictions to capture the first view of the full-length MetH and develop a model for conformational switching.