What are the structural dynamics involved in protein allostery and catalysis? How do flexible enzymes perform challenging chemistry? Can we animate crystal structures of proteins? These are outstanding questions in bi- ology, which motivate studies of proteins in motion. Capturing proteins in action is the next frontier of structural enzymology. By working at the interface of biochemistry and physical chemistry, we aim to go beyond the stat- ic picture of enzymes that is obtained by traditional Bragg diffraction and instead recover dynamic information with non-conventional X-ray scattering and diffraction approaches. We are particularly interested in enzymes of biomedical importance that have been challenging to study by traditional methods, such as drug targets that are allosterically regulated and enzymes that complex mechanisms to synthesize natural products with phar- maceutical potential.
Molecular motions play an important role in the regulation and function of enzymes. Capturing proteins in action is the next frontier of structural biology. New X-ray methods will allow us to visualize how proteins tune their activities and perform sequential reactions in the correct order.
|Parker, Mackenzie J; Maggiolo, Ailiena O; Thomas, William C et al. (2018) An endogenous dAMP ligand in Bacillus subtilis class Ib RNR promotes assembly of a noncanonical dimer for regulation by dATP. Proc Natl Acad Sci U S A 115:E4594-E4603|
|Shoemaker, Susannah C; Ando, Nozomi (2018) X-rays in the Cryo-Electron Microscopy Era: Structural Biology's Dynamic Future. Biochemistry 57:277-285|