- Trace Elements in Health
- Drug Transport and Resistance Mechanisms
- Metal complexes synthesis and properties
- Heavy Metal Exposure and Toxicity
- Electrochemical Analysis and Applications
- Alzheimer's disease research and treatments
- Lipid Membrane Structure and Behavior
- Iron Metabolism and Disorders
- Mass Spectrometry Techniques and Applications
- ATP Synthase and ATPases Research
- Molecular Sensors and Ion Detection
- Prion Diseases and Protein Misfolding
- Metalloenzymes and iron-sulfur proteins
- Ion Transport and Channel Regulation
- Advanced battery technologies research
- Plant Micronutrient Interactions and Effects
- Supramolecular Self-Assembly in Materials
- Advanced biosensing and bioanalysis techniques
- Nanocluster Synthesis and Applications
- Corrosion Behavior and Inhibition
- DNA and Biological Computing
- Receptor Mechanisms and Signaling
- Photoreceptor and optogenetics research
- Amyotrophic Lateral Sclerosis Research
- DNA and Nucleic Acid Chemistry
The University of Texas at Dallas
2017-2024
The University of Texas at Austin
2021
California Institute of Technology
2012-2015
Howard Hughes Medical Institute
2012-2015
Danish National Research Foundation
2013-2015
Aarhus University
2013-2015
National Research Foundation
2014
University of Zurich
2005-2012
Hebrew University of Jerusalem
2009
Friedrich-Alexander-Universität Erlangen-Nürnberg
2009
Significance Impaired copper regulation has been implicated in a range of human diseases, yet the current mechanistic understanding intracellular homeostasis remains incomplete. While Cu(I)-selective synthetic fluorescent probes could shed light on within living cells by dynamically reporting Cu(I) availability, affinity previously employed was insufficient to achieve significant metallation presence glutathione (GSH) at normal physiological concentrations. Employing an air-stable...
Dysregulation of copper and zinc homeostasis in the brain plays a critical role Alzheimer disease (AD). Copper binding to amyloid-beta peptide (Abeta) is linked with neurotoxicity Abeta free radical damage. Metallothionein-3 (MT-3) small cysteine- metal-rich protein expressed found down-regulated AD. This occurs intra- extracellularly, it an important metabolism copper. In cell cultures Zn7MT-3, by unknown mechanism, protects neurons from toxicity Abeta. We have, therefore, used range...
Abstract Artificial native-like lipid bilayer systems constructed from phospholipids assembling into unilamellar liposomes allow the reconstitution of detergent-solubilized transmembrane proteins supramolecular lipid-protein assemblies called proteoliposomes, which mimic cellular membranes. Stabilization these complexes remains challenging because their chemical composition, hydrophobicity and structural instability membrane proteins, lability interactions between protein, detergent, lipids...
The design, synthesis, and properties of a new gadolinium-based copper-responsive magnetic resonance imaging (MRI) contrast agent is presented. sensor (GdL1) has high selectivity for copper ions exhibits 43% increase in r1 relaxivity (20 MHz) upon binding to 1 equiv Cu2+ aqueous buffer. Interestingly, the presence physiological levels human serum albumin (HSA), amplified further up 270%. Additional spectroscopic X-ray absorption spectroscopy (XAS) studies show that coordinated by two...
Copper complexes are of medicinal and biological interest, including as anticancer drugs designed to cleave intracellular biomolecules by O2 activation. To exhibit such activity, the copper complex must be redox active resistant dissociation. Metallothioneins (MTs) glutathione (GSH) abundant in cytosol nucleus. Because they thiol-rich reducing molecules with high CuI affinity, potential competitors for a ion bound drug. Herein, we report investigation panel /CuII often used drugs, diverse...
Metallothioneins (MTs) are a ubiquitous class of small metal-binding proteins involved in metal homeostasis and detoxification.
Abstract In eukaryotes, iron-sulfur clusters are essential cofactors for numerous physiological processes, but these primarily biosynthesized in mitochondria. Previous studies suggest mitochondrial ABCB7-type exporters involved maturation of cytosolic proteins. However, the molecular mechanism how participate this process remains elusive. Here, we report a series cryo-electron microscopy structures eukaryotic homolog human ABCB7, CtAtm1, determined at average resolutions ranging from 2.8 to...
Abstract Copper is essential for living cells, yet toxic at elevated concentrations. Class 1B P-type (P -) ATPases are present in all kingdoms of life, facilitating cellular export transition metals including copper. follow an alternating access mechanism, with inward-facing E1 and outward-facing E2 conformations. Nevertheless, no structural information on states available P -ATPases, hampering mechanistic understanding. Here, we structures that reach 2.7 Å resolution a copper-specific...
Protein design is challenging as it requires simultaneous consideration of interconnected factors, such fold, dynamics, and function. These evolutionary constraints are encoded in protein sequences can be learned through the latent generative landscape (LGL) framework to predict functional by leveraging patterns, enabling exploration uncharted sequence space. By simulating designed proteins molecular dynamics (MD), we gain deeper insights into interdependencies governing structure dynamics....