A5037288851- Alzheimer's disease research and treatments
- bioluminescence and chemiluminescence research
- Tryptophan and brain disorders
- Protein Structure and Dynamics
- Protein Interaction Studies and Fluorescence Analysis
- Photoreceptor and optogenetics research
- Advanced biosensing and bioanalysis techniques
- Protein purification and stability
- Enzyme Structure and Function
- Monoclonal and Polyclonal Antibodies Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Computational Drug Discovery Methods
- Glycosylation and Glycoproteins Research
- Advanced Electron Microscopy Techniques and Applications
- Molecular Sensors and Ion Detection
- Metabolomics and Mass Spectrometry Studies
- Electrochemical sensors and biosensors
- Light effects on plants
- Enzyme Catalysis and Immobilization
- Photosynthetic Processes and Mechanisms
- Lanthanide and Transition Metal Complexes
- Viral Infectious Diseases and Gene Expression in Insects
- Nicotinic Acetylcholine Receptors Study
University of Pavol Jozef Šafárik
2017-2025
Bioscience (Slovakia)
2020-2025
University Hospital Brno
2021-2023
St. Anne's University Hospital Brno
2021-2023
Masaryk University
2021-2023
Abstract Background Apolipoprotein E (ApoE) ε4 genotype is the most prevalent risk factor for late-onset Alzheimer’s Disease (AD). Although ApoE4 differs from its non-pathological ApoE3 isoform only by C112R mutation, molecular mechanism of proteinopathy unknown. Methods Here, we reveal aggregation using a combination experimental and computational techniques, including X-ray crystallography, site-directed mutagenesis, hydrogen-deuterium mass spectrometry (HDX-MS), static light scattering...
NanoLuc, a superior β-barrel fold luciferase, was engineered 10 years ago but the nature of its catalysis remains puzzling. Here experimental and computational techniques are combined, revealing that imidazopyrazinone luciferins bind to an intra-barrel catalytic site also allosteric shaped on enzyme surface. Structurally, binding prevents simultaneous site, vice versa, through concerted conformational changes. We demonstrate restructuration can boost luminescent reaction in remote active...
Abstract X-ray crystallography has tremendously served structural biology by routinely providing high-resolution 3D structures of macromolecules. The extent information encoded in the is proportional to which resolution crystals diffract and structure can be refined to. Therefore, there a continuous effort obtain high-quality crystals, especially for those proteins, are considered difficult crystallize into protein suitable sizes crystallography. Efforts enhancing have also been made...
X-ray crystallography is an established tool to probe the structure of macromolecules with atomic resolution. Compared alternative techniques such as single-particle cryo-electron microscopy and micro-electron diffraction, uniquely suited room-temperature studies for obtaining a detailed picture subjected external electric field (EEF). The impact EEF on proteins has been extensively explored through single-crystal crystallography, which works well larger high-quality protein crystals. This...
Abstract Monoclonal antibodies of the immunoglobulin G (IgG) type have become mainstream therapeutics for treatment many life‐threatening diseases. For their successful application in clinic and a favorable cost‐benefit ratio, design formulation these therapeutic molecules must guarantee long‐term stability an extended period time. Accelerated studies, e.g., by employing thermal denaturation, great potential enabling high‐throughput screening campaigns to find optimal molecular variants...
Biophysical properties of antibody-based biopharmaceuticals are a critical part their release criteria. In this context, finding the appropriate formulation is equally important as optimizing intrinsic biophysical through protein engineering, and both mutually dependent. Most previous studies have empirically tested impact additives on measures colloidal stability, while mechanistic aspects usually been limited to only thermodynamic stability protein. Here we emphasize kinetic irreversible...
Abstract NanoLuc, a superior β-barrel fold luciferase, was engineered 10 years ago but the nature of its catalysis remains puzzling. Here experimental and computational techniques were combined, revealing that imidazopyrazinone luciferins bind to an intra-barrel catalytic site also allosteric shaped on enzyme surface. Binding prevents simultaneous binding site, vice versa, through concerted conformational changes. We demonstrate restructuration can dramatically boost luminescent reaction in...
Alzheimer’s disease (AD) is a chronic neurodegenerative associated with the overproduction and accumulation of amyloid-β peptide hyperphosphorylation tau proteins in brain. Despite extensive research on amyloid-based mechanism AD pathogenesis, underlying cause remains poorly understood. No disease-modifying therapies currently exist, numerous clinical trials have failed to demonstrate any benefits. The recent discovery that has antimicrobial activities supports possibility...
Abstract NanoLuc, a superior β-barrel fold luciferase, was engineered 10 years ago but the nature of its catalysis remains puzzling. Here experimental and computational techniques were combined, revealing that imidazopyrazinone luciferins bind to an intra-barrel catalytic site also allosteric shaped on enzyme surface. Structurally, binding prevents simultaneous site, vice versa , through concerted conformational changes. We demonstrate restructuration can boost luminescent reaction in remote...
Abstract Background Apolipoprotein E (ApoE) ε4 genotype is the most prevalent risk factor for late-onset Alzheimer’s Disease (AD). Although ApoE4 differs from its non-pathological ApoE3 isoform only by C112R mutation, molecular mechanism of proteinopathy unknown. Methods Here, we reveal aggregation using a combination experimental and computational techniques, including X-ray crystallography, site-directed mutagenesis, hydrogen-deuterium mass spectrometry (HDX-MS), static light scattering...
Abstract Objective Although the link between microbial infections and Alzheimer’s disease (AD) has been demonstrated in multiple studies, involvement of pathogens development AD remains unclear. Therefore, this theory beckons further systematic investigation. In study, we have examined association 10 most widely discussed viral bacterial found serum cerebrospinal fluid (CSF) from patients with AD. Methods We used an in-house developed multiplex PCR kit for simultaneous detection five CSF 50...