A5002753894- Protein Kinase Regulation and GTPase Signaling
- Melanoma and MAPK Pathways
- Cancer Mechanisms and Therapy
- Computational Drug Discovery Methods
- Cancer-related Molecular Pathways
- Enzyme Structure and Function
- Microtubule and mitosis dynamics
- Plant Micronutrient Interactions and Effects
- Photosynthetic Processes and Mechanisms
- Cancer-related gene regulation
- X-ray Spectroscopy and Fluorescence Analysis
- Lanthanide and Transition Metal Complexes
- Cellular transport and secretion
- Protein Tyrosine Phosphatases
- Iron Metabolism and Disorders
- Nuclear Physics and Applications
- Iron oxide chemistry and applications
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Advanced Breast Cancer Therapies
- Protein Degradation and Inhibitors
- Electron Spin Resonance Studies
- Genomics and Phylogenetic Studies
University of Minnesota
2018-2024
University of Minnesota System
2024
Twin Cities Orthopedics
2022-2023
University of Wisconsin–La Crosse
2017-2018
Significance Many drugs trigger changes to the structure of their target receptor upon binding. These conformational effects are thought be an essential part molecular recognition but have proven challenging quantify. Using a high-throughput method for tracking structural in protein kinase solution, we discovered that many clinically important cancer substantial Aurora A, and these systematically account ability differentiate between different biochemical forms A. The results provide insight...
Abstract Compared to most ATP-site kinase inhibitors, small molecules that target an allosteric pocket have the potential for improved selectivity due often observed lower structural similarity at these distal sites. Despite their promise, relatively few examples of structurally confirmed, high-affinity inhibitors exist. Cyclin-dependent 2 (CDK2) is a many therapeutic indications, including non-hormonal contraception. However, inhibitor against this with exquisite has not reached market...
The type II class of RAF inhibitors currently in clinical trials paradoxically activate BRAF at subsaturating concentrations. Activation is mediated by induction dimers, but why activation rather than inhibition occurs remains unclear. Using biophysical methods tracking dimerization and conformation, we built an allosteric model inhibitor-induced that resolves the contributions inhibitor binding to two active sites dimer, revealing key differences between I inhibitors. For coupling...
The type II class of RAF inhibitors currently in clinical trials paradoxically activate BRAF at subsaturating concentrations. Activation is mediated by induction dimers, but why activation rather than inhibition occurs remains unclear. Using biophysical methods tracking dimerization and conformation, we built an allosteric model inhibitor-induced that resolves the contributions inhibitor binding to two active sites dimer, revealing key differences between I inhibitors. For coupling...
ABSTRACT The type II class of RAF inhibitors currently in clinical trials paradoxically activate BRAF at subsaturating concentrations. Activation is mediated by induction dimers, but why activation rather than inhibition occurs remains unclear. Using biophysical methods tracking dimerization and conformation we built an allosteric model inhibitor-induced that resolves the contributions inhibitor binding to two active sites dimer, revealing key differences between I inhibitors. For coupling...
Abstract Compared to most ATP-site kinase inhibitors, small molecules that target an allosteric pocket have the potential for improved selectivity due often observed lower structural similarity at these distal sites. Despite their promise, relatively few examples of structurally confirmed, high-affinity inhibitors exist. Cyclin-dependent 2 (CDK2) is a many therapeutic indications, including non-hormonal contraception. 1 However, inhibitor against this with exquisite has not reached market...
The type II class of RAF inhibitors currently in clinical trials paradoxically activate BRAF at subsaturating concentrations. Activation is mediated by induction dimers, but why activation rather than inhibition occurs remains unclear. Using biophysical methods tracking dimerization and conformation we built an allosteric model inhibitor-induced that resolves the contributions inhibitor binding to two active sites dimer, revealing key differences between I inhibitors. For coupling...
The divalent magnesium cation (Mg 2+ ) is imperative to the survival of all living organisms on earth. It stabilizes different macromolecular and cellular structures, plays a vital role in vast number essential biochemical reactions. Due its significance, many have evolved complex systems adapt varying environmental levels Mg . Additionally, ability environments with limiting required by bacteria cause disease humans. Gaining insight into how maintain homeostasis when deficient will provide...
Living cells require magnesium ions for many fundamental biochemical processes. Certain pathogenic bacteria can thrive in environments with limiting magnesium, and the ability to adapt limitation be critical bacterial virulence. We have used genetic approaches gain insight into how Salmonella enterica , a major cause of food‐borne illness, adapts low magnesium. Using screen mutant defective adaptation we identified periplasmic lipoprotein protein that promotes growth This protein, which has...