A5074611451- Biochemical and Molecular Research
- Enzyme Structure and Function
- Colorectal Cancer Treatments and Studies
- Pharmacological Effects of Natural Compounds
- HIV/AIDS drug development and treatment
- Folate and B Vitamins Research
- Crystallization and Solubility Studies
- Cancer, Hypoxia, and Metabolism
- X-ray Diffraction in Crystallography
- Alzheimer's disease research and treatments
- Protein Structure and Dynamics
- Cancer Research and Treatments
- Cancer-related Molecular Pathways
- Computational Drug Discovery Methods
- RNA and protein synthesis mechanisms
- Crystallography and molecular interactions
- Genetic Neurodegenerative Diseases
- Microtubule and mitosis dynamics
- Structural and Chemical Analysis of Organic and Inorganic Compounds
- Enzyme Catalysis and Immobilization
- DNA and Nucleic Acid Chemistry
- Molecular Sensors and Ion Detection
- Photosynthetic Processes and Mechanisms
- GABA and Rice Research
- Synthesis and Properties of Aromatic Compounds
University of Warmia and Mazury in Olsztyn
2025
Instytut Biologii Doświadczalnej im. Marcelego Nenckiego
2011-2022
Polish Academy of Sciences
2005-2021
University of Warsaw
1994-2016
The GRHL2 gene, encoding the Grainyhead-like 2 transcription factor, is essential for various biological processes. While has a complex role in cancer biology, its genetic variants have been also implicated different forms of hearing loss (HL), including autosomal dominant non-syndromic (DFNA28). Here, we report novel c.1061C>T, p.(Ala354Val) mutation within DNA binding domain (DBD) that was identified three-generation HL family using targeted multi-gene panel covering 237 HL-related genes....
Enzymes involved in thymidylate biosynthesis, synthase (TS), and dihydrofolate reductase (DHFR) are well-known targets cancer chemotherapy. In this study, we demonstrated for the first time, that human TS DHFR form a strong complex vitro co-localize normal colon cell cytoplasm nucleus. Treatment of cells with methotrexate or 5-fluorouracil did not affect distribution either enzyme within cells. However, 5-FU, but MTX, lowered presence DHFR-TS nucleus by 2.5-fold. The results may suggest...
The crystal structure of mouse thymidylate synthase (mTS) in complex with substrate dUMP and antifolate inhibitor Raltitrexed is reported. reveals, for the first time group mammalian TS structures, a well-ordered segment 13 N-terminal amino acids, whose ordered conformation stabilized due to specific packing. consists two homodimers, differing conformation, one being more closed (dimer AB) thus supporting tighter binding ligands, other open CD) allowing weaker ligands. This difference...
Abstract LGMD2L is a subtype of limb-girdle muscular dystrophy (LGMD), caused by recessive mutations in ANO5 , encoding anoctamin-5 (ANO5). We present the analysis five patients with skeletal muscle weakness for whom heterozygous within were identified whole exome sequencing (WES). Patients varied age disease onset (from 22 to 38 years) and severity morphological clinical phenotypes. Out nine detected one was novel (missense p.Lys132Met, accompanied p.His841Asp) not yet characterized...
Endogenous thymidylate synthases, isolated from tissues or cultured cells of the same specific origin, have been reported to show differing slow-binding inhibition patterns. These were reflected by biphasic linear dependence inactivation rate on time and accompanied parameters. Considering its importance for chemotherapeutic drug resistance, possible effect synthase post-translational modification was tested, e.g. phosphorylation, comparing sensitivities two inhibitors, 5-fluoro-dUMP...
Fibrillation of β ‐amyloid is recognized as a key process leading to the development Alzheimer's disease. Small peptides called ‐sheet breakers were found inhibit fibrillation and dissolve amyloid fibrils in vitro , vivo cell culture studies [1,2]. The mechanism by which peptide inhibition takes place remains elusive detailed model needs be established. Here, we present new insights into possible role consecutive Phe residues, structure breakers, supported results obtained means MD...
Crystal structures of mouse thymidylate synthase (mTS) in complexes with (1) sulfate anion, (2) 2′-deoxyuridine 5′-monophosphate (dUMP) and (3) 5-fluoro-dUMP (FdUMP) N 5,10-methylenetetrahydrofolate (meTHF) have been determined deposited Protein Data Bank under the accession codes 3IHI, 4E5O 5FCT, respectively. The show a strong overall similarity to corresponding rat human synthases (rTS hTS, respectively). Unlike whose unliganded liganded forms assume different conformations ("inactive"...
Alzheimer's disease is a fatal neurodegenerative malady which up to very recently did not have approved therapy modifying its course. After controversial approval of aducanumab (monoclonal antibody clearing β-amyloid plaques) by FDA for use in early stages disease, possibly new avenue opened the treatment patients. In line with this approach search compounds blocking aggregation into amyloid oligomers subsequently forming fibrils or helping getting rid plaques formed fibrils. Here we present...
Abstract β‐sheet breakers (BSB) constitute a class of peptide inhibitors amyloidogenesis, process which is hallmark many diseases called amyloidoses, including Alzheimer's disease (AD); however, the molecular details their action are still not fully understood. Here we describe results computational investigation three BSBs, iaβ6 (LPFFFD), iaβ5 (LPFFD), and iaβ6_Gly (LPFGFD), in complex with fibril model Aβ42 propose kinetically probable mechanism action. The involves binding BSB to central...
Highly purified preparations of thymidylate synthase, isolated from calf thymus, and L1210 parental FdUrd-resistant cells, were found to be nitrated, as indicated by a specific reaction with anti-nitro-tyrosine antibodies, suggesting this modification appear endogenously in normal tumor tissues. Each human, mouse Ceanorhabditis elegans recombinant TS preparation, incubated vitro the presence NaHCO3, NaNO2 H2O2 at pH 7.5, underwent tyrosine nitration, leading Vmaxapp 2-fold lower following...
Abstract To solve the inhibition mechanism of thymidylate synthase (TS) by N 4 -hydroxy-dCMP (N -OH-dCMP), crystallographic studies were undertaken. Structures three mouse TS (mTS) complexes with inhibitor solved, based on crystals formed enzyme protein in presence either only -OH-dCMP [crystal A, belonging to space group C 1 2 1, two monomers asymmetric unit (ASU), measured 1.75 Å resolution] or both and 5,10 - methylenetetrahydrofolate (mTHF) (crystals B C, 21, each a single monomer ASU,...