In this study, we were first to structurally analyze inositol phosphates (IPs) synthesized by three mammalian isoforms of inositol hexakisphosphate kinase (IP6K) from IP5 and IP6. The NMR and mass analyses revealed a number of products with diverse, yet specific, stereochemistry, defined by the architecture of IP6K's active site. We showed that IP6K synthesizes both pyrophosphate (diphospho) as well as triphospho groups on the inositol ring. All three IP6K isoforms share the same activities both in vitro and in vivo.
COBISS.SI-ID: 3889434
We determined the crystal structure of the full-length and sole cAMP phosphodiesterase, Rv0805 from M. tuberculosis. The dimeric core catalytic domain of Rv0805 adopts a metallophosphoesterase fold, and the unique C-terminal region builds the active site and contributes to multiple substrate utilization and directs the localization of Rv0805 to the cell. Expression of Rv0805 in M. smegmatis alters cell permeability to hydrophobic cytotoxic compounds. Rv0805 may therefore play a key role in the pathogenicity of mycobacteria, either by hydrolyzing cAMP, or by altering cell wall functioning.
COBISS.SI-ID: 4259610
The "4D Biology Workshop for Health and Disease" aimed at finding the best organizing principles for large-scale proteomics, interactomics and structural genomics/biology initiatives, and setting the vision for future high-throughput research and large-scale data gathering in biological and medical science. The workshop provided a strong basis for creating major possibilities in advancing research and clinical applications towards personalized medicine.
COBISS.SI-ID: 4515866
Inositol is a precursor of many biologically active substances, like polyphosphoinositol lipids and inositol (poly)phosphates. Naturally most abundant is inositol hexakisphosphate (IP6) or phytic acid, which is famous for its positive effects on organisms. Medically interesting is also IP6 precursor, inositol-pentoxiphosphate (IP5), showing specific proapoptotic and antiangiogenic properties. IP5 and IP6 are precursors of higher inositol pyrophosphates. These molecules can nonenyzmatically phosphorylate specific pre-phosphorylated proteins, which represents a novel mode of cell signaling.
COBISS.SI-ID: 4248090
EPR/FTIR characterization of the lipid membranes that facilitate ostreolysin binding showed that the average membrane fluidity of ostreolysin-susceptible liposomes alone cannot account for the membrane activity of the protein. EPR spectra strongly suggest that chemical properties of membrane constituents, their specific distribution, and physical characteristics of membrane nanodomains, resulting from the presence of sterol and sphingomyelin (or a highly ordered phospholipid, dipalmitoylphosphatidylcholine), are essential prerequisites for ostreolysin membrane binding and pore-formation.
COBISS.SI-ID: 2185551