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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Unknown (R35)
Project #
5R35GM124847-03
Application #
9771492
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Smith, Ward
Project Start
2017-08-01
Project End
2022-07-31
Budget Start
2019-08-01
Budget End
2020-07-31
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Cornell University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
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