A5008227797- Alzheimer's disease research and treatments
- Computational Drug Discovery Methods
- Ion Transport and Channel Regulation
- Cholinesterase and Neurodegenerative Diseases
- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Trace Elements in Health
- Drug Transport and Resistance Mechanisms
- Sulfur Compounds in Biology
- Heat shock proteins research
- Amino Acid Enzymes and Metabolism
- Prion Diseases and Protein Misfolding
- Bacterial Genetics and Biotechnology
- Enzyme Structure and Function
- RNA Interference and Gene Delivery
- Nitric Oxide and Endothelin Effects
- DNA and Nucleic Acid Chemistry
- Hemoglobin structure and function
- Cancer Research and Treatments
- thermodynamics and calorimetric analyses
- RNA modifications and cancer
- ATP Synthase and ATPases Research
- Ion channel regulation and function
- Endoplasmic Reticulum Stress and Disease
- DNA Repair Mechanisms
Engelhardt Institute of Molecular Biology
2016-2025
Kazan Federal University
2022-2024
Federal Research Centre of Nutrition and Biotechnology
2024
Russian Academy of Sciences
2009-2020
St Petersburg University
2020
Howard Hughes Medical Institute
2020
Institute of Cytology
2020
New York University
2020
Klinik für Frauenheilkunde
2020
München Klinik
2020
Na,K-ATPase is highly sensitive to changes in the redox state, and yet mechanisms of its sensitivity remain unclear. We have explored possible involvement S-glutathionylation catalytic α subunit redox-induced responses. For first time, presence S-glutathionylated cysteine residues was shown duck salt glands, rabbit kidneys, rat myocardium. Exposure oxidized glutathione (GSSG) resulted an increase number residues. Increase associated with dose- time-dependent suppression enzyme function up...
OPINION article Front. Genet., 15 May 2017Sec. Genetics of Aging Volume 8 - 2017 | https://doi.org/10.3389/fgene.2017.00058
Fast changes in environmental oxygen availability translate into shifts mitochondrial free radical production. An increase intraerythrocytic reduced glutathione (GSH) during deoxygenation would support the detoxification of exogenous oxidants released circulation from hypoxic peripheral tissues. Although reported, mechanism behind this acute oxygen-dependent regulation GSH red blood cells remains unknown. This study explores role hemoglobin (Hb) modulation levels cells. We have demonstrated...
Alzheimer's disease (AD) is a multifactorial systemic that triggered, at least in part, by the accumulation of β-amyloid (Aβ) peptides brain, but it also depends on immune system-mediated regulation. Recent studies suggest B cells may play role AD development and point to clonally expanded patients. However, specificity unknown, contribution Aβ-specific pathology unclear. In this study, we have developed novel method identify flow cytometry using fluorescent tetramers. The suggested enables...
In recent years, a number of synthetic potentiators antibiotics have been discovered. Their action can significantly enhance the antibacterial effect and limit spread antibiotic resistance through inhibition bacterial cystathionine-γ-lyase. To expand known set potentiators, we developed methods for synthesis five new representatives 6-bromoindole derivatives—potential inhibitors cystathionine-γ-lyase—namely potassium 3-amino-5-((6-bromoindolyl)methyl)thiophene-2-carboxylate (MNS2) its...
Tubulins are among the most successful targets for cancer chemotherapy. However, emergence of drug resistance stimulates continuous search novel chemotherapeutics. Here, we discover that coumarin-30, a widely available laser dye, binds to colchicine site tubulin and inhibits microtubule dynamics cell division at submicromolar concentrations. By combining coumarin-30 as fluorescent probe with microscale thermophoresis approach, develop versatile assay detecting tubulin–ligand interactions...
Tubulins are among the most successful targets for cancer chemotherapy. However, emergence of drug resistance stimulates continuous search novel chemotherapeutics. Here, we discover that coumarin-30, a widely available laser dye, binds to colchicine site tubulin and inhibits microtubule dynamics cell division at submicromolar concentrations. By combining coumarin-30 as fluorescent probe with microscale thermophoresis approach, develop versatile assay detecting tubulin–ligand interactions...
Human papillomavirus type 16 (HPV16) belongs to viruses of the high-risk and is associated by overexpression E6 E7 oncoproteins, which determine oncogenic properties virus, such as immortalization malignant transformation proliferating epithelial cells. The biogenesis redox-sensitive proteins at early stages viral infection leads blocking cell antioxidant defense system ubiquintin-dependent degradation p53 Rb tumor suppressors. Maintaining high rates proliferation contributes an increase in...
Cystathionine-γ-lyase (CSE) is a key enzyme for H2S generation in the pathogenic bacteria Staphylococcus aureus, Pseudomonas aeruginosa, etc. Suppression of CSE activity significantly increases antibiotic susceptibility bacteria. In this work method to synthesize novel indole-based inhibitor, 3-ammo-5-[(6-bromo-1H-indol-1-yl)methyl]thiophene, named MNS1, has been developed. The synthesis MNS1 based on modification substituted thiophene as main structural fragment, which involved alkylation...
GTP hydrolysis catalyzed in the ribosome by a complex of two polypeptide release factors, eRF1 and eRF3, is required for fast efficient termination translation eukaryotes. Here, isothermal titration calorimetry used quantitative thermodynamic characterization eRF3 interactions with guanine nucleotides, Mg2+. We show that (i) binds GDP (K(d) = 1.9 microM) this interaction depends only minimally on Mg(2+) concentration; (ii) to 0.5 presence Mg2+ (iii) displaces from eRF1*eRF3*GDP complex, vice...
AbstractSome RNases selectively attack malignant cells, triggering an apoptotic response, and therefore are considered as alternative chemotherapeutic drugs. Here we studied the effects of Bacillus intermedius RNase (binase) on murine myeloid progenitor cells FDC-P1; transduced FDC-P1 ectopically expressing mutated human KIT N822K oncogene and/or AML1-ETO oncogene; leukemia Kasumi-1 both these oncogenes. Expression oncogenes makes sensitive to toxic binase. were most responsive actions...
Igs offer a versatile template for combinatorial and rational design approaches to the de novo creation of catalytically active proteins. We have used covalent capture selection strategy identify biocatalysts from within human semisynthetic antibody variable fragment library that uses nucleophilic mechanism. Specific phosphonylation at single tyrosine light-chain framework was confirmed in recombinant IgG construct. High-resolution crystallographic structures unmodified phosphonylated Fabs...
The triggers of late-onset sporadic Alzheimer's disease (AD) are still poorly understood. Impairment protein phosphorylation with age is well-known; however, the role in β-amyloid peptide (Aβ) not studied sufficiently. Zinc-induced oligomerization Aβ represents a potential seeding mechanism for formation neurotoxic oligomers and aggregates. Phosphorylation by Ser8 (pS8-Aβ), localized inside zinc-binding domain peptide, may significantly alter its zinc-induced oligomerization. Indeed, using...
Abstract By maintaining the Na + and K transmembrane gradient mammalian Na,K-ATPase acts as a key regulator of neuronal electrotonic properties. has an important role in synaptic transmission memory formation. Accumulation beta-amyloid (Aβ) at early stages Alzheimer’s disease is accompanied by reduction functional activity. The molecular mechanism behind this phenomenon not known. Here we show that monomeric Aβ(1-42) forms tight ( d 3 μM), enthalpy-driven equimolar complex with α1β1...
Neuronal cell death at late stages of Alzheimer’s disease (AD) causes the release cytosolic proteins. One most abundant such proteins, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), forms stable aggregates with extracellular amyloid-β (Aβ). We detect these in cerebrospinal fluid (CSF) from AD patients levels directly proportional to progressive AD. found that GAPDH a covalent bond Q15 Aβ is mediated by transglutaminase (tTG). The Q15A substitution weakens interaction between and reduces...
β-Amyloid aggregation on living cell surfaces is described as responsible for the neurotoxicity associated with different neurodegenerative diseases. It suggested that of β-amyloid (Aβ) peptide neuronal surface leads to various deviations its vital function due myriad pathways defined by internalization calcium ions, apoptosis promotion, reduction membrane potential, synaptic activity loss, etc. These are structural reorganizations and pathologies cytoskeleton mainly involving actin...
Exogenous ribonucleases are known to inhibit tumor growth via apoptosis induction in cells, allowing consider them as promising anticancer drugs for clinical application. In this work the antitumor potential of binase was evaluated vivo and mechanism cytotoxic effect on cells comprehensively studied vitro. We investigated tumoricidal activity using three murine models Lewis lung carcinoma (LLC), lymphosarcoma RLS 40 melanoma B-16. show first time that intraperitoneal injection at a dose...
Ion pump, Na,K‐ATPase specifically binds cardiotonic steroids (CTS), which leads to inhibition of the enzyme activity and activation signaling network in cell. We have studied interaction with CTS two different types – marinobufagenin ouabain. shown that both inhibit same K i values, but binding ouabain is sensitive conformation while not. Furthermore, results structural changes Na,K‐ATPase. Our data allow explain diversity effects on receptor function caused by CTS.