A5041484309- Enzyme function and inhibition
- Protein Structure and Dynamics
- Alzheimer's disease research and treatments
- Synthesis and Catalytic Reactions
- S100 Proteins and Annexins
- Advanced NMR Techniques and Applications
- Phenothiazines and Benzothiazines Synthesis and Activities
- thermodynamics and calorimetric analyses
- Heat shock proteins research
- Advanced MRI Techniques and Applications
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Protein Interaction Studies and Fluorescence Analysis
- Biochemical and Molecular Research
- Parkinson's Disease Mechanisms and Treatments
- Polyamine Metabolism and Applications
- Mass Spectrometry Techniques and Applications
- Connexins and lens biology
- Analytical Chemistry and Chromatography
- Lipid Membrane Structure and Behavior
- Ion channel regulation and function
- Lanthanide and Transition Metal Complexes
- DNA and Nucleic Acid Chemistry
- Prion Diseases and Protein Misfolding
- Hemoglobin structure and function
- Protein purification and stability
Vilnius University
2011-2024
Czech Academy of Sciences, Institute of Biotechnology
2024
Latvijas Organiskās Sintēzes Institūts
2017-2024
University of Copenhagen
2013
Abstract Membrane proteins are targets of most available pharmaceuticals, but they difficult to produce recombinantly, like many other aggregation-prone proteins. Spiders can silk at huge concentrations by sequestering their regions in micellar structures, where the very soluble N-terminal domain (NT) forms shell. We hypothesize that fusion NT could similarly solubilize non-spidroin proteins, and design a charge-reversed mutant (NT*) is pH insensitive, stabilized hypersoluble compared...
Understanding the connection between protein structure and function requires a quantitative understanding of electrostatic effects. Structure-based calculations are essential for this purpose, but their use has been limited by long-standing discussion on which value to dielectric constants (ε(eff) ε(p)) required in Coulombic Poisson-Boltzmann models. The currently used values ε(eff) ε(p) essentially empirical parameters calibrated against thermodynamic properties that indirect measurements...
The formation of amyloid fibril plaques in the brain creates inflammation and neuron death. This process is observed neurodegenerative disorders, such as Alzheimer’s Parkinson’s diseases. Alpha-synuclein main protein found neuronal inclusions patients who have suffered from disease. S100A9 a calcium-binding, pro-inflammation protein, which also plaques. To understand influence on aggregation α-synuclein, we analyzed their co-aggregation kinetics resulting structure by Fourier-transform...
Human heat shock protein 90 (Hsp90) is a key player in the homeostasis of proteome and plays role numerous diseases, such as cancer. For design Hsp90 ATPase activity inhibitors, it important to understand relationship between an inhibitor structure its inhibition potential. The volume binding one most parameters that are rarely being studied. Here, volumes several ligands recombinant were obtained by three independent experimental techniques: fluorescent pressure shift assay, vibrating tube...
We designed novel pre-drug compounds that transform into an active form covalently modifies particular His residue in the site, a difficult task to achieve, and applied carbonic anhydrase (CAIX), transmembrane protein, highly overexpressed hypoxic solid tumors, important for cancer cell survival proliferation because it acidifies tumor microenvironment helping invasion metastases processes. The have several functionalities: (1) primary sulfonamide group recognizing anhydrases (CA), (2)...
S100A9 is a pro-inflammatory protein that co-aggregates with other proteins in amyloid fibril plaques. can influence the aggregation kinetics and structure of alpha-synuclein (α-syn), which involved Parkinson's disease. Currently, there are limited data regarding their cross-interaction how it influences process. In this work, we analyzed interaction using solution 19F 2D 15N-1H HSQC NMR spectroscopy studied properties these two proteins. Here, show α-syn interacts at specific regions, also...
The change in protein volume observed upon protein-ligand interaction (termed as the binding volume) is an important but largely neglected thermodynamic parameter from perspective of both fundamental science and potential applications development specific ligands. pressure derivative Gibbs energy, thus elevated required to determine volumetric properties proteins. Here we describe use high-pressure spectrofluorimetry unfolding ligand binding- induced changes a protein. degree at pressures...
Prion diseases are associated with conformational conversion of cellular prion protein into a misfolded pathogenic form, which resembles many properties amyloid fibrils. The same sequence can misfold different conformations, responsible for variations in disease phenotypes (prion strains). In this work, we use atomic force microscopy, FTIR spectroscopy and magic-angle spinning NMR to devise structural models mouse fibrils prepared three denaturing conditions. We find that the fibril core...
<title>Abstract</title> The α-synuclein (α-syn) amyloid fibrils are involved in various neurogenerative diseases. Solid-state NMR (ssNMR) has been showed as a powerful tool to study a-syn aggregates. Here, we report the <sup>1</sup>H, <sup>13</sup>C and <sup>15</sup>N back-bone chemical shifts of new α-syn polymorph obtained using proton-detected ssNMR spectroscopy under fast (95 kHz) magic angle spinning conditions. manual shift assignments were cross-validated FLYA algorithm. secondary...
ABSTRACT We designed novel pre-drug compounds that transform into an active form covalently modifies particular His residue in the site, a difficult task to achieve, and applied carbonic anhydrase (CAIX), transmembrane protein, highly overexpressed hypoxic solid tumors, important for cancer cell survival proliferation because it acidifies tumor microenvironment helping invasion metastases processes. The have several functionalities: 1) primary sulfonamide group recognizing anhydrases (CA),...
We designed novel pre-drug compounds that transform into an active form covalently modifies particular His residue in the site, a difficult task to achieve, and applied carbonic anhydrase (CAIX), transmembrane protein, highly overexpressed hypoxic solid tumors, important for cancer cell survival proliferation because it acidifies tumor microenvironment helping invasion metastases processes. The have several functionalities: 1) primary sulfonamide group recognizing anhydrases (CA), 2)...
We designed novel pre-drug compounds that transform into an active form covalently modifies particular His residue in the site, a difficult task to achieve, and applied carbonic anhydrase (CAIX), transmembrane protein, highly overexpressed hypoxic solid tumors, important for cancer cell survival proliferation because it acidifies tumor microenvironment helping invasion metastases processes. The have several functionalities: (1) primary sulfonamide group recognizing anhydrases (CA), (2)...
We designed novel pre-drug compounds that transform into an active form covalently modifies particular His residue in the site, a difficult task to achieve, and applied carbonic anhydrase (CAIX), transmembrane protein, highly overexpressed hypoxic solid tumors, important for cancer cell survival proliferation because it acidifies tumor microenvironment helping invasion metastases processes. The have several functionalities: 1) primary sulfonamide group recognizing anhydrases (CA), 2)...
Proteins undergo changes in their partial volumes numerous biological processes such as enzymatic catalysis, unfolding–refolding, and ligand binding. The change the protein volume upon binding—a parameter termed protein–ligand binding volume—can be extensively studied by high-pressure NMR spectroscopy. In this study, we developed a method to determine from single two-dimensional (2D) 1H–15N heteronuclear quantum coherence (HSQC) spectrum at different pressures, if exchange between...
Protein–ligand binding volumes were determined in the FPSA experiment by varying both ligand and GdmHCl concentrations. GdmHCl-induced unfolding pathways of carbonic anhydrase isoforms II XIII differ from isoform I.