Papers by Nurbubu Moldogazieva
This Dataset contains input and output files, along with trajectories of molecular dynamics simul... more This Dataset contains input and output files, along with trajectories of molecular dynamics simulation linked to the research article entitled "Elucidating human alpha-fetoprotein binding sites and their affinities to estrogens and antiestrogens by in silico modeling and point mutagenesis." by Nurbubu T. Moldogazieva, Daria S. Ostroverkhova, Vladimir V. Kadochnikov, Innokenty M. Mokhosoev, Alexander A. Terentiev, Yuri B. Porozov
Biochemical and Biophysical Research Communications
EC Pharmacology and Toxicology, May 27, 2021
Antioxidants
Short linear motifs (SLiMs) are evolutionarily conserved functional modules of proteins composed ... more Short linear motifs (SLiMs) are evolutionarily conserved functional modules of proteins composed of 3 to 10 residues and involved in multiple cellular functions. Here, we performed a search for SLiMs that exert sequence similarity to two segments of alpha-fetoprotein (AFP), a major mammalian embryonic and cancer-associated protein. Biological activities of the peptides, LDSYQCT (AFP14–20) and EMTPVNPGV (GIP-9), have been previously confirmed under in vitro and in vivo conditions. In our study, we retrieved a vast array of proteins that contain SLiMs of interest from both prokaryotic and eukaryotic species, including viruses, bacteria, archaea, invertebrates, and vertebrates. Comprehensive Gene Ontology enrichment analysis showed that proteins from multiple functional classes, including enzymes, transcription factors, as well as those involved in signaling, cell cycle, and quality control, and ribosomal proteins were implicated in cellular adaptation to environmental stress condition...
Metabolites
Short linear motifs (SLiMs) are evolutionarily conserved functional modules of proteins that repr... more Short linear motifs (SLiMs) are evolutionarily conserved functional modules of proteins that represent amino acid stretches composed of 3 to 10 residues. The biological activities of two short peptide segments of human alpha-fetoprotein (AFP), a major embryo-specific and cancer-related protein, have been confirmed experimentally. This is a heptapeptide segment LDSYQCT in domain I designated as AFP14–20 and a nonapeptide segment EMTPVNPGV in domain III designated as GIP-9. In our work, we searched the UniprotKB database for human proteins that contain SLiMs with sequence similarity to the both segments of human AFP and undertook gene ontology (GO)-based functional categorization of retrieved proteins. Gene set enrichment analysis included GO terms for biological process, molecular function, metabolic pathway, KEGG pathway, and protein–protein interaction (PPI) categories. We identified the SLiMs of interest in a variety of non-homologous proteins involved in multiple cellular process...
Journal of Biomolecular Structure and Dynamics, 2017
Short linear motifs (SLiMs) have been recognized to perform diverse functions in a variety of reg... more Short linear motifs (SLiMs) have been recognized to perform diverse functions in a variety of regulatory proteins through the involvement in protein-protein interactions, signal transduction, cell cycle regulation, protein secretion, etc. However, detailed molecular mechanisms underlying their functions including roles of definite amino acid residues remain obscure. In our previous studies, we demonstrated that conformational dynamics of amino acid residues in oligopeptides derived from regulatory proteins such as alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and pregnancy specific β1-glycoproteins (PSGs) contributes greatly to their biological activities. In the present work, we revealed the 22-member linear modules composed of direct and reverse AFP 14-20-like heptapeptide motifs linked by CxxGY/FxGx consensus motif within epidermal growth factor (EGF), growth factors of EGF family and numerous regulatory proteins containing EGF-like modules. We showed, first, the existence of similarity in amino acis signatures of both direct and reverse motifs in terms of their physicochemical properties. Second, molecular dynamics (MD) simulation study demonstrated that key receptor-binding residues in human EGF in the aligned positions of the direct and reverse motifs may have similar distribution of conformational probability densities and dynamic behaviour despite their distinct physicochemical properties. Third, we found that the length of a polypeptide chain (from 7 to 53 residues) has no effect, while disulfide bridging and backbone direction significantly influence the conformational distribution and dynamics of the residues. Our data may contribute to the atomic level structure-function analysis and protein structure decoding; additionally, they may provide a basis for novel protein/peptide engineering and peptide-mimetic drug design.
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Biomedit͡sinskai͡a khimii͡a
Alpha-fetoprotein (AFP) is the major mammalian fetal protein and the recognized tumor marker. Thi... more Alpha-fetoprotein (AFP) is the major mammalian fetal protein and the recognized tumor marker. This review summarizes data on structure and function of AFP with emphasis on human AFP, which is intensively investigated. During the last decade multiple functionally important sites of human AFP have been revealed or predicted by searching of similarity between primary structures of AFP and other proteins or their DNA sequences. A number of peptides derived from human AFP have been studied by different teams of investigators. These peptides were obtained by limited proteolysis of AFP or synthesized using solid phase chemistry. Study of biological (physiological) activities of these peptides allows determining biologically active sites of alpha-fetoprotein and constructing its structural and functional map. Biomodulating properties of these peptides make them a potential basis for design of drugs for different purposes including using in anticancer therapy. Conformational changes in AFP m...
Biochimie, 2021
The concept of oxidative distress had arisen from the assessment of cellular response to high con... more The concept of oxidative distress had arisen from the assessment of cellular response to high concentrations of reactive species that result from an imbalance between oxidants and antioxidants and cause biomolecular damage. The intracellular distribution and flux of reactive species dramatically change in time and space contributing to the remodeling of the redox landscape and sensitivity of protein residues to oxidants. Here, we hypothesize that compromised spatiotemporal control of generation, conversions, and removal of reactive species underlies protein damage and dysfunction of protein degradation machineries. This leads to the accumulation of oxidatively damaged proteins resulted in an age-dependent decline in the organismal adaptability to oxidative stress. We highlight recent data obtained with the use of various cell cultures, animal models, and patients on irreversible and non-repairable oxidation of key redox-sensitive residues. Multiple reaction products include peptidyl hydroperoxides, alcohols, carbonyls, and carbamoyl moieties as well as Tyr-Tyr, Trp-Tyr, Trp-Trp, Tyr-Cys, His-Lys, His-Arg, and Tyr-Lys cross-links. These lead to protein fragmentation, misfolding, covalent cross-linking, oligomerization, aggregation, and ultimately, causing impaired protein function and turnover. 20S proteasome and autophagy-lysosome pathways are two major types of machinery for the degradation and elimination of oxidatively damaged proteins. Spatiotemporal dysregulation of these pathways under oxidative distress conditions is implicated in aging and age-related disorders such as neurodegenerative and cardiovascular diseases and diabetes. Future investigations in this field allow the discovery of new drugs to target components of dysregulated cell signaling and protein degradation machinery to combat aging and age-related chronic diseases.
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Papers by Nurbubu Moldogazieva