A5101496900- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Sesame and Sesamin Research
- Plant Genetic and Mutation Studies
- RNA and protein synthesis mechanisms
- Neuroscience and Neural Engineering
- Cardiac electrophysiology and arrhythmias
- Chemical Reactions and Isotopes
- Electrochemical Analysis and Applications
- Peanut Plant Research Studies
- Chemical Synthesis and Analysis
- Agricultural Science and Fertilization
- Nicotinic Acetylcholine Receptors Study
- Mitochondrial Function and Pathology
- Photoreceptor and optogenetics research
- Genetic Neurodegenerative Diseases
- RNA modifications and cancer
- Click Chemistry and Applications
- Protein Structure and Dynamics
- Tryptophan and brain disorders
- Spectroscopy and Quantum Chemical Studies
- Microfluidic and Capillary Electrophoresis Applications
- Ion Channels and Receptors
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
University of Iowa
2021-2025
University of Houston
2018-2024
Baylor College of Medicine
2022-2024
Arizona State University
2013-2023
University of Wisconsin–Madison
2010-2021
Washington University in St. Louis
2020
Center for Molecular Medicine and Immunology
2020
BioEnergetics (United States)
2013-2018
Vollum Institute
2016-2018
Oregon Health & Science University
2015-2018
Voltage-gated ion channels are crucial for electrical activity and chemical signaling in a variety of cell types. Structure-activity studies involving electrophysiological characterization mutants widely used allow us to quickly realize the energetic effects mutation by measuring macroscopic currents fitting observed voltage dependence conductance Boltzmann equation. However, such an approach is somewhat limiting, principally because inherent assumption that channel activation two-state...
Plasmids containing 23S rRNA randomized at positions 2057–2063 and 2502–2507 were introduced into Escherichia coli, affording a library of clones which produced modified ribosomes in addition to the pre-existing wild-type ribosomes. These screened with derivative puromycin, natural product acts as an analogue 3′-end aminoacyl-tRNA terminates protein synthesis by accepting growing polypeptide chain, thereby killing bacterial cells. The puromycin this study contained dipeptide...
In an earlier study, β3-puromycin was used for the selection of modified ribosomes, which were utilized incorporation five different β-amino acids into Escherichia coli dihydrofolate reductase (DHFR). The selected ribosomes able to incorporate structurally disparate DHFR, in spite use a single puromycin individual clones. this we examine extent structure employed ribosome influences regio- and stereochemical preferences during protein synthesis; mechanistic probe suppressor tRNACUA activated...
The hallmark of many intracellular pore blockers such as tetra-alkylammonium compounds and local anesthetics is their ability to allosterically modify the movement voltage sensors in voltage-dependent ion channels. For instance, sensor domain III specifically stabilized activated state when sodium currents are blocked by anesthetics. molecular mechanism underlying this long-range interaction between blocker-binding site remains poorly understood. Here, using scanning mutagenesis combination...
Membrane proteins are uniquely placed at the interface of internal and external milieu cells, many them unsurprisingly function as signal transducers involved in pathways critical for normal physiological activity. A majority these membrane have a modular architecture with
Many ion channels are modulated by multiple stimuli, which allow them to integrate a variety of cellular signals and precisely respond physiological needs. Understanding how these different signaling pathways interact has been challenge in part because the complexity underlying models. In this study, we analyzed energetic relationships polymodal using linkage principles. We first show that proteins dually voltage ligand, net free-energy change can be obtained measuring charge-voltage (Q-V)...
The introduction of noncanonical amino acids into proteins and peptides has been great interest for many years facilitated the detailed study peptide/protein structure mechanism. In addition to numerous nonproteinogenic α-l-amino acids, bacterial ribosome modification provided wherewithal enable synthesis with a much greater range structural diversity, as use endogenous in reconstituted protein synthesizing systems. recent report, elongation factor P (EF-P), putatively essential enabling...
Steroid receptor coactivator 3 (SRC-3) is a critical mediator of many intracellular signaling pathways that are crucial for cancer proliferation and metastasis. In this study, we performed structure–activity relationship exploration drug-like optimization the hit compound SI-2, guided by in vitro/in vivo metabolism studies cytotoxicity assays. Our efforts led to discovery two lead compounds, SI-10 SI-12. Both compounds exhibit potent against panel human cell lines demonstrate acceptable...
Although many redox signaling molecules are present at low concentrations, typically ranging from micromolar to submicromolar levels, they often play essential roles in a wide range of biological pathways and disease mechanisms. However, accurately measuring low-abundant analytes has been significant challenge due the lack sensitivity quantitative capability existing measurement methods. In this study, we introduced novel chemically induced amplifiable system for quantifying low-abundance...
Cooperative interactions mediate information transfer between structural domains of a protein molecule and are major determinants function modulation. The prevalent theories to understand the thermodynamic origins cooperativity have been developed reproduce complex behavior global observable such as ligand binding or enzyme activity. However, in most cases measurement single cannot uniquely define all terms that fully describe energetics system. Here we establish theoretical groundwork for...
For ascertaining component (s) maximizing yield, 21 genotypes (parental cultivar and 20 macromutants) of sesame (Sesamum indicum. L., var - B-67, Family: Pedaliaceae) were analyzed based on genetic parameters viz . variability, character association path analysis considering seven yield related traits (plant height, number primary branches/plant, total distance from base to first branching, capsules main axis, capsules/plant capsule length) (seed yield/seed protein content/seed fatty oil...
Signaling proteins such as ion channels largely exist in two functional forms, corresponding to the active and resting states, connected by multiple intermediates. Multiparametric kinetic models based on sophisticated electrophysiological experiments have been devised identify molecular interactions of these conformational transitions. However, this approach is arduous not suitable for large-scale perturbation analysis interaction pathways. Recently, we described a model-free method obtain...
Described herein are the synthesis and photophysical characterization of a library aryl-substituted oxazole- thiazole-based dipeptidomimetic analogues, their incorporation into position 66 green fluorescent protein (GFP) in lieu natural fluorophore. These analogues resemble fluorophore formed naturally by GFP. As anticipated, properties varied as function substituents at para phenyl ring. The fluorescence emission wavelength maxima compounds from ∼365 nm (near-UV region) to ∼490 (visible...