Transient and heterogeneous protein interactions play important roles both in the catalytic and regulatory functions of protein complexes and multi-modular machinery. However, the technical challenges involved in structural characterizations of such systems have placed critical barriers against understanding their intrinsic behavior. The vitamin B12-dependent methionine synthase and class Ia ribonucleotide reductases are two enzymes that epitomize such systems where structural insight into their multiple conformations will advance our understanding of their physiological and medically relevant behavior. To meet the technical challenge of investigating these systems, I will exploit the ensemble structural information that can be gained by small- and wide-angle X-ray scattering and employ mathematical methods to deconvolute the mixtures into quantifiable individual states. This work will be complemented by crystallography, spectroscopy, and analytical ultracentrifugation.

Public Health Relevance

Ribonucleotide reductase is a protein found in all organisms that is an important target for cancer drugs, and methionine synthase is an important protein in healthy pregnancies. By investigating the structure of these floppy proteins that have been challenging to study, we will gain better insight into drug design targeting ribonucleotide reductase and genetic mutations in methionine synthase.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Transition Award (R00)
Project #
Application #
Study Section
No Study Section (in-house review) (NSS)
Program Officer
Anderson, Vernon
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Princeton University
Schools of Arts and Sciences
United States
Zip Code
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
Davis, Katherine M; Schramma, Kelsey R; Hansen, William A et al. (2017) Structures of the peptide-modifying radical SAM enzyme SuiB elucidate the basis of substrate recognition. Proc Natl Acad Sci U S A 114:10420-10425
Meisburger, Steve P; Ando, Nozomi (2017) Correlated Motions from Crystallography beyond Diffraction. Acc Chem Res 50:580-583
Meisburger, Steve P; Thomas, William C; Watkins, Maxwell B et al. (2017) X-ray Scattering Studies of Protein Structural Dynamics. Chem Rev 117:7615-7672
Meisburger, Steve P; Taylor, Alexander B; Khan, Crystal A et al. (2016) Domain Movements upon Activation of Phenylalanine Hydroxylase Characterized by Crystallography and Chromatography-Coupled Small-Angle X-ray Scattering. J Am Chem Soc 138:6506-16
Rustiguel, Joane K; Soares, Ricardo O S; Meisburger, Steve P et al. (2016) Full-length model of the human galectin-4 and insights into dynamics of inter-domain communication. Sci Rep 6:33633
Ando, Nozomi; Li, Haoran; Brignole, Edward J et al. (2016) Allosteric Inhibition of Human Ribonucleotide Reductase by dATP Entails the Stabilization of a Hexamer. Biochemistry 55:373-81
Skou, Soren; Gillilan, Richard E; Ando, Nozomi (2014) Synchrotron-based small-angle X-ray scattering of proteins in solution. Nat Protoc 9:1727-39