A5078357534- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Enzyme Structure and Function
- Chemical Synthesis and Analysis
- DNA and Nucleic Acid Chemistry
- Bacterial Genetics and Biotechnology
- Mass Spectrometry Techniques and Applications
- Spectroscopy and Quantum Chemical Studies
- Glycosylation and Glycoproteins Research
- HIV Research and Treatment
- Enzyme Catalysis and Immobilization
- Bacteriophages and microbial interactions
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Enzyme Production and Characterization
- DNA Repair Mechanisms
- Viral Infections and Outbreaks Research
- Molecular spectroscopy and chirality
- RNA Interference and Gene Delivery
- RNA Research and Splicing
- Cellular transport and secretion
- Antimicrobial Peptides and Activities
- Sirtuins and Resveratrol in Medicine
- Genomics and Rare Diseases
- Viral Infections and Vectors
- Genomics and Chromatin Dynamics
Petersburg Nuclear Physics Institute
2015-2025
Peter the Great St. Petersburg Polytechnic University
2006-2025
Russian Scientific Center of Radiology and Surgical Technologies
2019-2025
Kurchatov Institute
2012-2024
Russian Academy of Sciences
2001-2012
European Molecular Biology Laboratory
2004
European Molecular Biology Laboratory
1999-2002
European Bioinformatics Institute
1998-1999
Pacific Institute of Bioorganic Chemistry. GB Elyakova Far Eastern Branch of the Russian Academy of Sciences
1995-1997
Midorigaoka Hospital
1996
HIV-1 transcription is activated by the viral Tat protein that recruits host positive elongation factor-b (P-TEFb) containing CDK9/cyclin T1 to promoter. P-TEFb in cells exists as a lower molecular weight dimer and high complex of 7SK RNA, T1, HEXIM1 several additional proteins. Our previous studies implicated CDK2 regulation. We also found inhibition iron chelators leads CDK9 activity, suggesting functional link between CDK9. Here, we investigate whether phosphorylates regulates its...
The RecX protein, a very active natural RecA protein inhibitor, can completely disassemble filaments at nanomolar concentrations that are two to three orders of magnitude lower than protein. Based on the structure complex with presynaptic filament, we designed short first in class α-helical peptide both inhibits activities vitro and blocks bacterial SOS-response vivo. was using SEQOPT, novel method for global sequence optimization α-helices. SEQOPT produces artificial sequences containing...
α-Helices are the most frequently occurring elements of secondary structure in water-soluble globular proteins. Their increased conformational stability is among main reasons for high thermal proteins thermophilic bacteria. In addition, α-helices often involved protein interactions with other proteins, nucleic acids, and lipids cell membranes. That why highly stable α-helical peptides used as active specific inhibitors protein-protein have recently found more applications medicine. Several...
Abstract Recent studies have pointed out the important role of local water structures in protein conformational stability. Here, we present an accurate and computationally effective way to estimate free energy contribution simplest structure motif–the bridge. Based on combination empirical parameters for accessible surface area explicit consideration all possible bridges with protein, introduce improved solvation model. We find that accounting bridge formation our model is essential...
To investigate the role of α helices in protein thermostability, we compared energy characteristics from thermophilic and mesophilic proteins belonging to four families known three-dimensional structure, for at least one member each family. The changes intrinsic free α-helix formation were estimated using statistical mechanical theory describing helix/coil transitions peptide [Munoz, V., Serrano, L. Nature Struc. Biol. 1:399–409, 1994; Munoz, J. Mol. 245:275–296, 1995; 245:297–308, 1995]....
Abstract A large variety of short biologically active peptides possesses antioxidant, antibacterial, antitumour, anti-ageing and anti-inflammatory activity, involved in the regulation neuro-immuno-endocrine system functions, cell apoptosis, proliferation differentiation. Therefore, mechanisms their biological activity are attracting increasing attention not only modern molecular biology, biochemistry biophysics, but also pharmacology medicine. In this work, we systematically analysed ability...
Despite considerable efforts, mTOR inhibitors have produced limited success in the clinic. To define vulnerabilities of mTORC1-addicted cancer cells and to find previously unknown therapeutic targets, we investigated mechanism piperlongumine, a small molecule identified chemical library screen specifically target with hyperactive mTORC1 phenotype. Sensitivity piperlongumine was dependent on its ability suppress RUVBL1/2-TTT, complex involved chromatin remodeling DNA repair. Cancer high...
Abstract H‐bonding between protein surface polar/charged groups and water is one of the key factors hydration. Here, we introduce an Accessible Surface Area (ASA) model for computationally efficient estimation a free energy water–protein at any given conformation. The H‐bonds estimated using empirical formulas describing probabilities hydrogen bond formation that were derived from molecular dynamics simulations molecules small protein, Crambin, Abyssinian cabbage ( Crambe abyssinica ) seed....
HIV-1 escapes antiretroviral drugs by integrating into the host DNA and forming a latent transcriptionally silent provirus. This provirus presents major hurdle in eradication cure. Transcriptional activation, which is prerequisite for reactivation of proviruses, impaired latently infected T cells due to lack transcription factors, primarily NF-κB P-TEFb (CDK9/cyclin T1). We others previously showed that protein phosphatase-1 (PP1) regulates modulating CDK9 phosphorylation. Recently we have...
Abstract The assumption that the intrinsic α‐helical propensities of amino acids are position independent was critical in several helix/coil transition theories. In first paper these series, we reported this is not case for Gly and nonpolar aliphatic (Val, Leu, Met, Ile). Here have analyzed helical noncharged polar residues (Ser, Thr, Asn, Gln) at different positions a model polyalanine‐based peptide. We found Thr more favorable (by ∼0.3 kcal/mol) N1 N2 than helix center, although Ser, Gln...
Abstract In this study, we have analyzed experimentally the helical intrinsic propensities of noncharged and nonaromatic residues at different C‐terminal positions (C1, C2, C3) an Ala‐based peptide. The effect was found to be complex, resulting in extra stabilization or destabilization, depending on guest amino acid position under consideration. Polar (Ser, Thr, Cys, Asn, Gln) acids Gly were significantly larger several compared with α‐helix center (−1.0 kcal/mole some cases). Some nonpolar...
Eukaryotic TIP49a (Pontin) and TIP49b (Reptin) AAA+ ATPases play essential roles in key cellular processes. How their weak ATPase activity contributes to important functions remains largely unknown difficult analyze because of the divergent properties proteins homo- hetero-oligomeric assemblies. To circumvent these complexities, we have analyzed single ancient TIP49 ortholog found archaeon Methanopyrus kandleri (mkTIP49). All-atom homology modeling molecular dynamics simulations validated by...
KED and EDR peptides prevent dendritic spines loss in amyloid synaptotoxicity vitro model of Alzheimer's disease (AD). The objective this paper was to study epigenetic mechanisms peptides' neuroprotective effects on neuroplasticity spine morphology an AD mouse model. Daily intraperitoneal administration the peptide 5xFAD mice from 2 4 months age at a concentration 400 μg/kg tended increase neuroplasticity. prevented 5xFAD-M mice. Their action's possible molecular were investigated by...
It was reported recently that the capping box sequences of four N-terminal residues are very important for stabilization α-helices in proteins and peptides. To elucidate factors affect short peptides by this motif, we analyzed conformational properties side chains five several analogs neuropeptide Y (NPY). The analysis revealed three previously unreported appear to be an α-helix: (a) a second hydrogen bond Ser, Thr, Cys; (b) long-range electrostatic interactions between first (N-cap) fifth...
Abstract The rational design of peptide and protein helices is not only practical importance for engineering but also a useful approach in attempts to improve our understanding folding. Recent modifications theoretical models helix‐coil transitions allow accurate predictions the helix stability monomeric peptides water provide new possibilities design. We report here method α‐helices proteins using AGADIR, statistical mechanical theory tunneling algorithm global optimization multidimensional...
HIV-1 transcription activator protein Tat is phosphorylated in vitro by CDK2 and DNA-PK on Ser-16 residue PKR Ser-46 residue. Here we analyzed phosphorylation cultured cells its functionality. Mass spectrometry analysis showed primarily cells. In vitro, CDK2/cyclin E predominantly PKR—Tat Ser-46. Alanine mutations of either or decreased overall phosphorylation. Phosphorylation was reduced treated a small molecule inhibitor and, to lesser extent, an DNA-PK. Conditional knock-downs inhibited...
Ebola virus (EBOV) infection causes severe hemorrhagic fever. EBOV transcription is controlled by host protein phosphatase 1 (PP1), which dephosphorylates VP30 protein. We previously developed 1E7-03, a compound targeting noncatalytic site of PP1 that induced phosphorylation and inhibited transcription. Here, we attempted to further improve was not stable in murine serum. High-throughput screening with EBOV–green fluorescent conducted on 72 1E7-03 analogs identified 6 best inhibitory the...
The DprA protein has been implicated in the protection of incoming DNA. However, presence dprA gene family members, also known as smf, across diverse bacterial species suggests a broader functionality for their products. We examined role Escherichia coli DprA/Smf homologue conjugation. Remarkably, Bacillus subtilis dprA/smf can complement an E. mutant, indicating interchangeability genes between competent and non-competent conjugational processes. forms complex with DNA, facilitating...
Abstract A new method for approximate analytical calculations of solvent accessible surface area (SASA) arbitrary molecules and their gradients with respect to atomic coordinates was developed. This is based on the recursive procedure pairwise joining neighboring atoms. Unlike other available methods SASA calculations, has no empirical parameters, therefore can be used comparable accuracy in folded unfolded conformations macromolecules any chemical nature. As shown by tests globular proteins...