Prion diseases are fatal transmissible neurodegenerative diseases. The normal prion protein (PrP) converts into a pathological aggregated form, PrPSc, which is enriched in the ß-sheet structure, however the structure of the converted form of PrP remains inaccessible to high resolution techniques. By designed tethering of selected secondary structure elements we show that separation and swapping of subdomains of the globular domain is necessary for conversion and that domain-swapped dimer of PrP precedes amyloid formation and represents a potential target for therapeutic intervention.
COBISS.SI-ID: 4602394
In this article in the respected journal in the field of immunology, we reported the discovery of the mechanism of action antimalarials that are similar to quinacrin. In contrast to the prevailing opinion in literature we discovered that these inhibitors at therapeutic concentrations do not prevent endosomal acidification but directly bind to the nucleic acid. In this way they prevent the nucleic acid to activate endosomal TLRs such as TLR3, TLR7 and TLR9. The result is a significant particularly for the improvement of treatment of diseases characterized by activation of TLR9, 7, 8 and 3.
COBISS.SI-ID: 2971761
During the evolution of multi-cellular organisms more strict control over the metabolic flux through glycolysis became important. A key regulatory enzyme of glycolysis is 6-phosphofructo-1-kinase (PFK1) that is less inhibited by citrate in microbial organisms while in vertebrates it is strongly inhibited by specific effectors, including citrate. By substituting a single amino acid as a component of the allosteric citrate binding site in the human muscle PFK-M with the residue in the corresponding site of the fungal enzyme, the inhibitory effect was attenuated.
COBISS.SI-ID: 4531226
Surfaces exhibiting antimicrobial activity were prepared for potential medical application to prevent microbial biofilm formation on medical devices, such as catheters and implants. On a model substrate a silane coating with reactive epoxy groups was prepared, which enable binding of the antimicrobial lipopeptide polymyxin B to the surface. The covalent binding prevented peptide leakage into the environment; however, its activity after binding has not been lost. The obtained material exhibited strong biocidic activity as shown against the Gram-negative bacterium Escherichia coli.
COBISS.SI-ID: 4471578
The article describes epitope mapping of a PrPSc-specific monoclonal antibody, which does not discriminate a conformational change between cellular (PrPC) and pathological (PrPSc) prion protein isoform, as described previously. By using phage display technology and molecular biology methods, a new C-terminally truncated fragment, PrP226, was determined in TSE infected samples.
COBISS.SI-ID: 27952345