A5023320155- Alzheimer's disease research and treatments
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Computational Drug Discovery Methods
- RNA Interference and Gene Delivery
- Ion Transport and Channel Regulation
- Cholinesterase and Neurodegenerative Diseases
- Enzyme Structure and Function
- Heat shock proteins research
- thermodynamics and calorimetric analyses
- ATP Synthase and ATPases Research
- RNA modifications and cancer
- Nitric Oxide and Endothelin Effects
- Ion channel regulation and function
- Hemoglobin structure and function
- Bacterial Genetics and Biotechnology
- Genetics, Aging, and Longevity in Model Organisms
- Viral Infectious Diseases and Gene Expression in Insects
- Advanced Biosensing Techniques and Applications
- Neuroscience of respiration and sleep
- Chemical Synthesis and Analysis
- Cancer Research and Treatments
- Antimicrobial Peptides and Activities
- Nicotinic Acetylcholine Receptors Study
- Protein Degradation and Inhibitors
Engelhardt Institute of Molecular Biology
2016-2025
National Research University Higher School of Economics
2012-2022
Russian Academy of Sciences
1997-2020
St Petersburg University
2020
Howard Hughes Medical Institute
2020
Institute of Cytology
2020
New York University
2020
Klinik für Frauenheilkunde
2020
München Klinik
2020
Klinikum rechts der Isar
2020
Abstract The net charge and isoelectric pH (pI) of a protein depend on the content ionizable groups their pK values. Ribonuclease Sa (RNase Sa) is an acidic with pI = 3.5 that contains no Lys residues. By replacing Asp Glu residues surface RNase residues, we have created 3K variant (D1K, D17K, E41K) 6.4 5K (3K + D25K, E74K) 10.2. We show values estimated using based model compound data can be in error by >1 unit, suggest how estimation improved. For variants, solubility, activity,...
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...
Abstract Glutathione (GSH) is the most abundant cellular antioxidant. As reactive oxygen species (ROS) are widely believed to promote aging and age-related diseases, antioxidants can neutralize ROS, it follows that GSH its precursor, N-acetyl cysteine (NAC), among popular dietary supplements. However, long- term effects of or NAC on healthy animals have not been thoroughly investigated. We employed C. elegans demonstrate chronic administration young aged perturbs global gene expression,...
The presence of a nucleotide binding site on hsp90 was very controversial until x-ray structure the N-terminal domain, showing nonconventional site, appeared. A recent study suggested that C-terminal domain also binds ATP (Marcu, M. G., Chadli, A., Bouhouche, I., Catelli, and Neckers, L. (2000) J. Biol. Chem. 275, 37181–37186). In this paper, interactions with native its recombinant (positions 1–221) 446–728) domains were studied by isothermal titration calorimetry, scanning differential...
To elucidate some aspects still debated concerning the interaction of Ca2+ and Mg2+ with CaM, thermodynamic binding parameters Ca2+−CaM Mg2+−CaM complexes were characterized by flow dialysis isothermal microcalorimetry under different experimental conditions. In particular, enthalpy entropy changes associated to their sites determined, allowing a better understanding mechanism underlying cation−CaM interactions. follows an enthalpy−entropy compensation relationship, suggesting that CaM...
A combination of explicit solvent molecular dynamics simulation (30 simulations reaching 4 µs in total), hybrid quantum mechanics/molecular mechanics approach and isothermal titration calorimetry was used to investigate the atomistic picture ion binding 15-mer thrombin-binding quadruplex DNA (G-DNA) aptamer. Binding ions G-DNA is complex multiple pathway process, which strongly affected by type cation. The individual ion-binding events are substantially modulated connecting loops aptamer,...
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...
Scanning microcalorimetry and circular dichroism were used to study conformational state heat denaturation of Ca2+-free synthetic calmodulin (SynCaM) three charge reversal mutants. We produced evidence for the major role electrostatic potential in stability flexibility SynCaM. The substitution 118DEE120 by 118KKK120 (SynCaM12A) does not influence protein; replacement 82EEE84 82KKK84 (SynCaM8) decreases its level, while combination these two mutations SynCaM18A significantly increases...
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...
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...
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...
During the 2010 Human Proteome Organization Congress in Sydney, a gene-centric approach emerged as feasible and tractable scaffold for assemblage of Project. Bringing principle into practice, roadmap 18th chromosome was drafted, postulating limited sensitivity analytical methods, serious bottleneck proteomics. In context problem, we refer to "copy number protein molecules" measurable assessment abundance. The is focused on development technology attain low- ultralow -"copied" portion...
Cholinergic dysfunction in Alzheimer’s disease (AD) can be mediated by the neuronal α7 nicotinic acetylcholine receptor (α7nAChR). Beta-amyloid peptide (Aβ) binds to α7nAChR, disrupting receptor’s function and causing neurotoxicity. In vivo not only Aβ but also its modified forms drive AD pathogenesis. One of these forms, iso-Aβ (containing an isomerized Asp7 residue), shows increased neurotoxicity vitro stimulates amyloidogenesis vivo. We suggested that such effects are α7nAChR-dependent....
Beta-amyloid peptide (Aβ) is a ligand associated with RAGE (Advanced glycosylation end product-specific receptor). Aβ translocated in complexes from the blood to brain across blood-brain barrier (BBB) by transcytosis. and its isoforms are important factors Alzheimer's disease (AD) pathogenesis. However, interaction was previously studied for but not isoforms. The present study has been directed at identifying key interfaces between (Aβ40, Aβ42, phosphorylated isomerized pS8-Aβ42,...
Beta amyloid peptide Aβ 1–42 (Aβ42) has a unique dual role in the human organism, as both with an important physiological function and one of most toxic biological compounds provoking Alzheimer's disease (AD). There are several known Aβ42 isoforms that we discuss here highly neurotoxic lead to early onset AD. is intrinsically disordered protein no experimentally solved structure under conditions. The objective this research was establish appropriate molecular dynamics (MD) methodology model...
Abstract Eukaryotic translational termination is triggered by polypeptide release factors eRF1, eRF3, and one of the three stop codons at ribosomal A‐site. Isothermal titration calorimetry shows that (i) separated MC, M, C domains human eRF1 bind to eRF3; (ii) GTP binding eRF3 requires complex formation with either MC or M + domains; (iii) domain interacts N (iv) Mg 2+ induce GTPase activity in ribosome. We suggest GDP site acquires an ability γ‐phosphate if altered cooperative action eRF1....