A5072314994- Enzyme Structure and Function
- Biochemical and Molecular Research
- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Colorectal Cancer Treatments and Studies
- Cancer, Hypoxia, and Metabolism
- Galectins and Cancer Biology
- Insect symbiosis and bacterial influences
- RNA Research and Splicing
- Cell death mechanisms and regulation
- Advanced NMR Techniques and Applications
- Pharmacological Effects of Natural Compounds
- Photosynthetic Processes and Mechanisms
- Erythrocyte Function and Pathophysiology
- Inflammasome and immune disorders
- Heat shock proteins research
- DNA Repair Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Mosquito-borne diseases and control
- RNA regulation and disease
University of North Carolina at Chapel Hill
2019-2025
University of Toronto
2024
Hospital for Sick Children
2024
The determination of a protein's structure is often first step towards the development mechanistic understanding its function. Considerable advances in computational protein prediction have been made recent years, with AlphaFold2 (AF2) emerging as primary tool used by researchers for this purpose. While AF2 generally predicts accurate structures folded proteins, we present here case where incorrectly small, and compact high confidence. This protein, pro-interleukin-18 (pro-IL-18), precursor...
Human thymidylate synthase (hTS) is essential for DNA replication and therefore a therapeutic target cancer. Effective targeting requires knowledge of the mechanism(s) regulation this 72 kDa homodimeric enzyme. Here, we investigate mechanism binding cooperativity nucleotide substrate. We have employed exquisitely sensitive methyl-based CPMG CEST NMR experiments enabling us to identify residues undergoing bifurcated linear 3-state exchange, including concerted switching between active...
Allostery is a major driver of biological processes requiring coordination. Thus, it one the most fundamental and remarkable phenomena in nature, there motivation to understand manipulate multitude ends. Today, often described terms two phenomenological models proposed more than half-century ago involving only T(tense) or R(relaxed) conformations. Here, methyl-based NMR provides extensive detail on dynamic T R switch classical dimeric allosteric protein, yeast chorismate mutase (CM), that...
Understanding how the crowded and complex cellular milieu affects protein stability dynamics has only recently become possible by using techniques such as in-cell nuclear magnetic resonance. However, combination of stabilizing destabilizing interactions makes simple predictions difficult. Here we show potential Danio rerio oocytes an resonance model that can be widely used to measure dynamics. We demonstrate in eukaryotic oocytes, which are 3–6-fold less than other cell types, attractive...
Abstract Human thymidylate synthase (hTS) is essential for DNA replication and therefore a therapeutic target cancer. Effective targeting requires knowledge of the mechanism(s) regulation this 72 kDa homodimeric enzyme. Here, we investigate mechanism binding cooperativity nucleotide substrate. We have employed exquisitely sensitive methyl-based CPMG CEST NMR experiments enabling us to identify residues undergoing bifurcated linear 3-state exchange, including concerted switching between...
Dynamics are often critical for biomolecular function. Herein we explore the role of motion in driving maturation process pro-IL-18, a potent pro-inflammatory cytokine that is cleaved by caspases-1 and -4 to generate mature form protein. An NMR dynamics study probing time scales over 12 orders magnitude focusing on 1H, 13C, 15N spin probes along protein backbone amino-acid side chains, reveals plastic structure, with millisecond scale occurring pair β-strands, β1 β*, show large structural...
Abstract Biomolecules continually sample alternative conformations. Consequently, even the most energetically favored ground conformational state has a finite lifetime. Here, we show that, in addition to 3D structure, lifetime of determines its biological activity. Using hydrogen-deuterium exchange nuclear magnetic resonance spectroscopy, found that Zika virus exoribonuclease-resistant RNA (xrRNA) encodes with is ~10 5 –10 7 longer than canonical base pairs. Mutations shorten apparent...