70,392 results match your criteria Biochemistry[Journal]


Mimicking Functions of Native Enzymes or Photosynthetic Reaction-Centers by Nucleoapzymes and Photonucleoapzymes.

Biochemistry 2020 Jul 2. Epub 2020 Jul 2.

The covalent linkage of catalytic units to aptamers-sequence-specific nucleic acids exhibiting selective binding affinities towards substrates leads to functional scaffolds mimicking native enzymes - nucleoapzymes. The binding of the substrates to the aptamer and their structural orientation in respect to the catalytic units duplicates the functions of the active center of enzymes. The possibility to link the catalytic sites directly, or through spacer units, to the 5'-end, 3'-end, and middle positions of the aptamers allows the design of nucleoapzyme libraries, revealing structure-functions diversities, and these can be modelled by molecular dynamics simulations. Read More

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http://dx.doi.org/10.1021/acs.biochem.0c00421DOI Listing

Thermodynamic and Kinetic Studies of the Nuclear Receptor Coactivator-4 (NCOA4) Interaction with Human Ferritin.

Biochemistry 2020 Jul 1. Epub 2020 Jul 1.

Ferritinophagy is a ferritin autophagic degradation process mediated by the selective Nuclear Receptor Coactivator-4 (NCOA4). NCOA4 binds to ferritin and delivers it to nascent autophagosomes, which then merge with the lysosomes for ferritin degradation and iron release. Earlier studies have demonstrated a specific association of NCOA4 with ferritin H-subunits, but not L-subunits. Read More

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http://dx.doi.org/10.1021/acs.biochem.0c00246DOI Listing

Energetics of ionized water molecules in the H-bond network near the Ca2+ and Cl- binding sites in photosystem II.

Biochemistry 2020 Jun 30. Epub 2020 Jun 30.

In photosystem II, water oxidation occurs at the oxygen-evolving complex (OEC). The presence of a hydronium ion (H3O+) was proposed at the Cl- binding site and Ca2+-depleted OEC. Using a quantum mechanical/molecular mechanical (QM/MM) approach, we report the stability of H3O+ in the PSII protein environment. Read More

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http://dx.doi.org/10.1021/acs.biochem.0c00177DOI Listing

Protein modifications critical for myonectin/erythroferrone secretion and oligomer assembly.

Biochemistry 2020 Jun 30. Epub 2020 Jun 30.

Myonectin/erythroferrone (also known as CTRP15) is a secreted hormone with metabolic function and a role in stress erythropoiesis. Despite its importance in physiologic processes, biochemical characterization of the protein is lacking. Here, we show that multiple protein modifications are critical for myonectin secretion and multimerization. Read More

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http://dx.doi.org/10.1021/acs.biochem.0c00461DOI Listing

Altered Drug Transport by Chloroquine Resistance Transporter Isoforms Harboring Mutations Associated with Piperaquine Resistance.

Biochemistry 2020 Jul 1. Epub 2020 Jul 1.

Department of Chemistry and Department of Biochemistry and Cellular and Molecular Biology, Georgetown University, Washington, D.C. 20057, United States.

Patterns of multiple amino acid substitutions in the chloroquine resistance transporter (PfCRT, UniProtKB Q8IBZ9) have previously been shown to mediate chloroquine resistance in malarial parasites. Recent reports suggest that novel mutations in PfCRT may mediate resistance to piperaquine (PPQ), which is used extensively as a partner drug in one prominent artemisinin combination therapy. How these novel PfCRT isoforms might mediate PPQ resistance (PPQR) is not known. Read More

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http://dx.doi.org/10.1021/acs.biochem.0c00247DOI Listing

Creation of Chitinase Producer and Disruption of Micromycete Cell Wall with the Obtained Enzyme Preparation.

Biochemistry (Mosc) 2020 Jun;85(6):717-724

Lomonosov Moscow State University, Faculty of Chemistry, Moscow, 119991, Russia.

A recombinant strain producing a complex of extracellular enzymes including chitinase from Myceliophtora thermophila was created based on the fungus Penicillium verruculosum. The activity of the enzyme preparations obtained from the cultural fluid of the producer strain was 0.55, 0. Read More

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http://dx.doi.org/10.1134/S0006297920060097DOI Listing

Effect of Cysteine Residue Substitution in the GCSAG Motif of the PMGL2 Esterase Active Site on the Enzyme Properties.

Biochemistry (Mosc) 2020 Jun;85(6):709-716

Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia.

The gene coding for PMGL2 esterase, which belongs to the family of mammalian hormone-sensitive lipases (HSLs), was discovered by screening a metagenomic DNA library from a permafrost soil. The active site of PMGL2 contains conserved GXSXG motif which includes Cys173 residue next to the catalytic Ser174. In order to clarify the functional role of the cysteine residue in the GCSAG motif, we constructed a number of PMGL2 mutants with Cys173 substitutions and studied their properties. Read More

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http://dx.doi.org/10.1134/S0006297920060085DOI Listing

Evolutionary Loss of the Ability of the Photosystem I Primary Electron Donor for the Redox Interaction with Mn-Bicarbonate Complexes.

Biochemistry (Mosc) 2020 Jun;85(6):697-708

Institute of Basic Biological Problems, Pushchino Scientific Center for Biological Research, Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia.

The structure and functional organization of the photosystem I (PSI) reaction center (RC) donor side has a significant similarity to the reaction centers of purple bacteria (bRCs), despite the fact that they belong to different types of RCs. Moreover, the redox potential values of their primary electron donors are identical (~0.5 V). Read More

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http://dx.doi.org/10.1134/S0006297920060073DOI Listing

Highly-Active Recombinant Formate Dehydrogenase from Pathogenic Bacterium Staphylococcus aureus: Preparation and Crystallization.

Biochemistry (Mosc) 2020 Jun;85(6):689-696

Lomonosov Moscow State University, Faculty of Chemistry, Moscow, 119991, Russia.

# These authors contributed equally to the work. NAD+-dependent formate dehydrogenase from Staphylococcus aureus (SauFDH) is one of the key enzymes responsible for the survival of this pathogen in the form of biofilms. 3D structure of the enzyme might be helpful in the search for highly specific SauFDH inhibitors that can be used as antibacterial agents exactly against S. Read More

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http://dx.doi.org/10.1134/S0006297920060061DOI Listing

Phycoerythrin Association with Photosystem II in the Cryptophyte Alga Rhodomonas salina.

Biochemistry (Mosc) 2020 Jun;85(6):679-688

Lomonosov Moscow State University, Faculty of Biology, Moscow, 119991, Russia.

# Deceased. Cryptophyte algae belong to a special group of oxygenic photosynthetic organisms containing pigment combination unique for plastids - phycobiliproteins and chlorophyll a/c-containing antenna. Despite the progress in investigation of morphological and ecological features, as well as genome-based systematics of cryptophytes, their photosynthetic apparatus remains poorly understood. Read More

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http://dx.doi.org/10.1134/S000629792006005XDOI Listing

Ommochromes from the Compound Eyes of Insects: Physicochemical Properties and Antioxidant Activity.

Biochemistry (Mosc) 2020 Jun;85(6):668-678

Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Moscow, 119334, Russia.

The objective of this study was screening of ommochromes from the compound eyes of insects and comparison of their antioxidant properties. Ommochromes were isolated in preparative quantities from insects of five different families: Stratiomyidae, Sphingidae, Blaberidae, Acrididae, and Tenebrionidae. The yield of ommochromes (dry pigment weight) was 0. Read More

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http://dx.doi.org/10.1134/S0006297920060048DOI Listing

Involvement of SASH1 in the Maintenance of Stable Cell-Cell Adhesion.

Biochemistry (Mosc) 2020 Jun;85(6):660-667

Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Moscow, 115478, Russia.

SASH1 is an adapter and signaling protein that contains SH3 and SAM domains responsible for protein-protein interactions. SASH1 downregulation has been observed in many tumors. We examined localization of SASH1 in cultures of normal IAR-20 epithelial cells and HT-29 colorectal cancer cells using immunofluorescence staining and confocal microscopy. Read More

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Manipulating Cellular Energetics to Slow Aging of Tissues and Organs.

Biochemistry (Mosc) 2020 Jun;85(6):651-659

Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, Moscow, 119991, Russia.

Up to now numerous studies in the field of gerontology have been published. Nevertheless, a well-known food restriction remains the most reliable and efficient way of lifespan extension. Physical activity is also a well-documented anti-aging intervention being especially efficient in slowing down the age-associated decline of skeletal muscle mass. Read More

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http://dx.doi.org/10.1134/S0006297920060024DOI Listing

The Role of Liquid-Liquid Phase Separation in the Compartmentalization of Cell Nucleus and Spatial Genome Organization.

Biochemistry (Mosc) 2020 Jun;85(6):643-650

Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334, Russia.

Functional compartmentalization of the cell nucleus plays an important role in the regulation of genome activity by providing accumulation of enzymes and auxiliary factors in the reaction centers, such as transcription factories, Cajal bodies, speckles, etc. The mechanisms behind the nucleus functional compartmentalization are still poorly understood. There are reasons to believe that the key role in the nucleus compartmentalization belongs to the process of liquid-liquid phase separation. Read More

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http://dx.doi.org/10.1134/S0006297920060012DOI Listing

Single Quantum Dot Tracking Unravels Agonist Effects on the Dopamine Receptor Dynamics.

Biochemistry 2020 Jun 25. Epub 2020 Jun 25.

Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37240, United States.

D2 dopamine receptors (DRD2s) belong to a family of G protein-coupled receptors that modulate synaptic dopaminergic tone via regulation of dopamine synthesis, storage, and synaptic release. DRD2s are the primary target for traditional antipsychotic medications; dysfunctional DRD2 signaling has been linked to major depressive disorder, attention-deficit hyperactivity disorder, addiction, Parkinson's, and schizophrenia. DRD2 lateral diffusion appears to be an important post-translational regulatory mechanism; however, the dynamic response of DRD2s to ligand-induced activation is poorly understood. Read More

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http://dx.doi.org/10.1021/acs.biochem.0c00360DOI Listing

Identifying structural determinants of product specificity in Leishmania major farnesyl diphosphate synthase.

Biochemistry 2020 Jun 25. Epub 2020 Jun 25.

Farnesyl diphosphate synthase (FPPS) is an isoprenoid chain elongation enzyme that catalyzes the sequential condensation of dimethylallyl diphosphate (DMAPP; C5) with isopentenyl diphosphate (IPP; C5) and the resulting geranyl diphosphate (GPP; C10) with another molecule of IPP, eventually producing farnesyl diphosphate (FPP; C15), which is a precursor for the biosynthesis of a vast majority of isoprenoids. Previous studies on FPPS have highlighted the importance of the structure around the hydrophobic chain elongation path in determining the product specificity. To investigate what structural features define the final chain length of the product in FPPS from Leishmania major, we designed and expressed six mutants of LmFPPS by replacing small amino acids around the binding pocket with bulky residues. Read More

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http://dx.doi.org/10.1021/acs.biochem.0c00432DOI Listing

Polysaccharide Sequence Influences the Specificity and Catalytic Activity of Glucuronyl C5-Epimerase.

Biochemistry 2020 Jun 29. Epub 2020 Jun 29.

Heparin is a widely used biotherapeutic produced from animal tissues. However, it might be possible to produce a bioengineered version using a multienzyme process, relying on the isolation of the K5 capsule heparosan and its chemical conversion to sulfoheparosan, NSH. Glucuronyl C5-epimerase, the first enzyme that acts on NSH, catalyzes the reversible conversion of glucuronic acid (GlcA) to iduronic acid (IdoA). Read More

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http://dx.doi.org/10.1021/acs.biochem.0c00419DOI Listing

Position-Dependent Effect of Guanine Base Damage and Mutations on Telomeric G-Quadruplex and Telomerase Extension.

Biochemistry 2020 Jun 29. Epub 2020 Jun 29.

Thomas C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, Maryland 21218, United States.

Telomeres are hot spots for mutagenic oxidative and methylation base damage due to their high guanine content. We used single-molecule fluorescence resonance energy transfer detection and biochemical assays to determine how different positions and types of guanine damage and mutations alter telomeric G-quadruplex structure and telomerase activity. We compared 15 modifications, including 8-oxoguanine (8oxoG), -6-methylguanine (O6mG), and all three possible point mutations (G to A, T, and C) at the 3' three terminal guanine positions of a telomeric G-quadruplex, which is the critical access point for telomerase. Read More

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http://dx.doi.org/10.1021/acs.biochem.0c00434DOI Listing

Molecular Basis for ADP-ribose Binding to the Mac1 Domain of SARS-CoV-2 Nsp3.

Biochemistry 2020 Jun 24. Epub 2020 Jun 24.

The virus that causes COVID-19, SARS-CoV-2, has a large RNA genome that encodes numerous pro-teins that might be targets for antiviral drugs. Some of these proteins, such as the RNA-dependent RNA polymerase, helicase and main protease, are well conserved between SARS-CoV-2 and the original SARS virus, but several others are not. This study examines one of the proteins encoded by SARS-CoV-2 that is most different, a macrodomain of nonstructural protein 3 (nsp3). Read More

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http://dx.doi.org/10.1021/acs.biochem.0c00309DOI Listing

Effect of Molecular Crowding on the Stability of RNA G-Quadruplexes with Various Numbers of Quartets and Lengths of Loops.

Biochemistry 2020 Jun 29. Epub 2020 Jun 29.

Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, 7-1-20 minatojima-Minamimachi, Kobe 650-0047, Japan.

G-Quadruplexes are noncanonical structures formed by guanine-rich regions of not only DNA but also RNA. RNA G-quadruplexes are widely present in the transcriptome as mRNAs and noncoding RNAs and take part in various essential functions in cells. Furthermore, stable RNA G-quadruplexes control the extent of biological functions, such as mRNA translation and antigen presentation. Read More

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http://dx.doi.org/10.1021/acs.biochem.0c00346DOI Listing

Bicarbonate-Mediated CO Formation on Both Sides of Photosystem II.

Biochemistry 2020 Jun 23. Epub 2020 Jun 23.

Department of Chemistry, Chemical Biological Centre, Umeå University, 90187 Umeå, Sweden.

The effect of bicarbonate (HCO) on photosystem II (PSII) activity was discovered in the 1950s, but only recently have its molecular mechanisms begun to be clarified. Two chemical mechanisms have been proposed. One is for the electron-donor side, in which mobile HCO enhances and possibly regulates water oxidation by acting as proton acceptor, after which it dissociates into CO and HO. Read More

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http://dx.doi.org/10.1021/acs.biochem.0c00208DOI Listing

The Proton Relay Network in the Bacterial P450s: CYP101A1 and CYP101D1.

Biochemistry 2020 Jun 23. Epub 2020 Jun 23.

Cytochrome P450s are amongst nature's most powerful catalysts. Their ability to activate molecular dioxygen to form high-valent ferryl intermediates (Compounds I and II) enables a wide array of chemistries ranging from simple epoxidations to more complicated C-H bond oxidation. Oxygen activation is achieved by reduction of the ferrous dioxygen complex, which requires electron transfer from a redox partner and subsequent double protonation to yield a water molecule and a ferryl porphyrin pi-cation radical (Compound I). Read More

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http://dx.doi.org/10.1021/acs.biochem.0c00329DOI Listing

Mitochondrial Transplantation: A Critical Analysis.

Authors:
B V Chernyak

Biochemistry (Mosc) 2020 May;85(5):636-641

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119234, Russia.

"Mitochondrial transplantation" refers to a procedure for introducing isolated mitochondria into a damaged area of a heart or other organ. A considerable amount of data has been accumulated on the therapeutic effects of "mitochondrial transplantation" in animals with ischemic heart damage. In 2017, the first attempts were made to apply this procedure in a clinic. Read More

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http://dx.doi.org/10.1134/S0006297920050132DOI Listing

Two Glycosyl 1-Phosphate Polymers and Teichulosonic Acid from Glutamicibacter protophormiae VKM Ac-2104 Cell Wall.

Biochemistry (Mosc) 2020 May;85(5):629-635

Lomonosov Moscow State University, Faculty of Biology, Moscow, 119991, Russia.

Two glycosyl 1-phosphate polymers containing monoglycosyl 1-phosphate, -6)-α-D-Glcp-(1-P-, and diglycosyl 1-phosphate, -6)-α-D-GalpNAc-(1→6)-α-D-GlcpNAc-(1-P-, in the repeating unit were identified in the cell wall of Glutamicibacter protophormiae VKM Ac-2104 (formerly, Arthrobacter protophormiae). The structures of these polymers were described for the first time in prokaryotes. Teichulosonic acid, the third identified polymer, with 3-deoxy-D-glycero-α-D-galacto-non-2-ulopyranosonic acid (Kdn) and β-D-glucopyranose residues in the main chain, →6)-β-D-Glcp-(1→8)-α-Kdn-(2→, has been previously detected in a number of actinobacteria. Read More

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http://dx.doi.org/10.1134/S0006297920050120DOI Listing

Melanin from the Lichens Cetraria islandica and Pseudevernia furfuracea: Structural Features and Physicochemical Properties.

Biochemistry (Mosc) 2020 May;85(5):623-628

Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of the Russian Academy of Sciences, Kazan, 420111, Russia.

Lichens are symbiotic photosynthesizing organisms with thalli formed by fungi and algae/cyanobacteria that possess high stress tolerance. One of the factors that contributes to the ability of a lichen to tolerate harsh environmental conditions is the presence of unique metabolites, including high-molecular-weight dark pigments termed melanins. The chemical composition and structure of lichen melanins remain poorly studied. Read More

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http://dx.doi.org/10.1134/S0006297920050119DOI Listing

Optimization of Method for Human Sex Determination Using Peptidome Analysis of Teeth Enamel from Teeth of Different Biological Generation, Archeological Age, and Degrees of Taphonomic Preservation.

Biochemistry (Mosc) 2020 May;85(5):614-622

Anuchin Research Institute and Museum of Anthropology, Lomonosov Moscow State University, Moscow, 125009, Russia.

Determination of biological sex to human remains is a fundamental requirement in anthropological, archeological, and forensic anthropological studies. Sex determination based on morphological criteria is significantly limited in the cases of juvenile remains and adult skeletons in a poor state of preservation. Regular attempts have been made to use alternative techniques to resolve this issue, including analysis of tooth enamel peptides by liquid chromatography/mass spectrometry. Read More

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http://dx.doi.org/10.1134/S0006297920050107DOI Listing

α-Synuclein Overexpression in SH-SY5Y Human Neuroblastoma Cells Leads to the Accumulation of Thioflavin S-positive Aggregates and Impairment of Glycolysis.

Biochemistry (Mosc) 2020 May;85(5):604-613

Lomonosov Moscow State University, Faculty of Bioengineering and Bioinformatics, Moscow, 119234, Russia.

Deterioration of energy metabolism in affected cells is an important feature of synucleinopathies, including Parkinson's disease. Here, we studied the association between α-synuclein accumulation and glycolysis using SH-SY5Y neuroblastoma cell lines stably expressing wild-type α-synuclein or its A53T mutant linked to the autosomal dominant form of the disease. Overexpression of both proteins led to the accumulation of thioflavin S-positive aggregates, more pronounced for α-synuclein A53T. Read More

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http://dx.doi.org/10.1134/S0006297920050090DOI Listing

Role of Arg243 and His239 Residues in the Recognition of Damaged Nucleotides by Human Uracil-DNA Glycosylase SMUG1.

Biochemistry (Mosc) 2020 May;85(5):594-603

Institute of Chemical Biology and Fundamental Medicine (ICBFM), Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russia.

Human uracil-DNA glycosylase SMUG1 removes uracil residues and some other noncanonical or damaged bases from DNA. Despite the functional importance of this enzyme, its X-ray structure is still unavailable. Previously, we performed homology modeling of human SMUG1 structure and suggested the roles of some amino acid residues in the recognition of damaged nucleotides and their removal from DNA. Read More

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http://dx.doi.org/10.1134/S0006297920050089DOI Listing

Lymphocyte Activation in the Development of Immune Tolerance in Women with Recurrent Pregnancy Loss.

Biochemistry (Mosc) 2020 May;85(5):583-593

National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Healthcare of the Russian Federation, Moscow, 117997, Russia.

Association between lymphocyte activation and formation of immune tolerance, as well as pregnancy outcome, in the case of immunocytotherapy (ICT) was studied in women with idiopathic recurrent pregnancy loss (IRPL). The content and phenotypic characteristics of activated T lymphocytes and NK cells were investigated in the peripheral blood of IRPL patients with different pregnancy outcomes (pregnancy prolongation to the full term and habitual miscarriage). The fraction of activated cells in the subpopulation of cytotoxic T lymphocytes (CD3CD8/CD3CD8CD69) before ICT was significantly lower in women who lost the pregnancy. Read More

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http://dx.doi.org/10.1134/S0006297920050077DOI Listing

Effect of His-tag Position on the Expression and Properties of Phenylacetone Monooxygenase from Thermobifida fusca.

Biochemistry (Mosc) 2020 May;85(5):575-582

Lomonosov Moscow State University, Faculty of Chemistry, Moscow, 119234, Russia.

Phenylacetone monooxygenase (EC 1.14.13. Read More

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http://dx.doi.org/10.1134/S0006297920050065DOI Listing

Mechanisms of Acinetobacter baumannii Capsular Polysaccharide Cleavage by Phage Depolymerases.

Biochemistry (Mosc) 2020 May;85(5):567-574

Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, 119991, Russia.

Aerobic gram-negative bacterium Acinetobacter baumannii has recently become one of the most relevant pathogens associated with hospital-acquired infections worldwide. A. baumannii produces a capsule around the cell, which represents a thick viscous layer of structurally variable capsular polysaccharide (CPS). Read More

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http://dx.doi.org/10.1134/S0006297920050053DOI Listing

Immune Response and Protective Efficacy of Inactivated and Live Influenza Vaccines Against Homologous and Heterosubtypic Challenge.

Biochemistry (Mosc) 2020 May;85(5):553-566

Chumakov Federal Scientific Center for Research and Development of Immune and Biological Products, Russian Academy of Sciences, Moscow, 108819, Russia.

Inactivated (whole-virion, split, subunit, and adjuvanted) vaccines and live attenuated vaccine were tested in parallel to compare their immunogenicity and protective efficacy. Homologous and heterosubtypic protection against the challenge with influenza H5N1 and H1N1 viruses in a mouse model were studied. Single immunization with live or inactivated whole-virion H5N1 vaccine elicited a high level of serum antibodies and provided complete protection against the challenge with the lethal A/Chicken/Kurgan/3/05 (H5N1) virus, whereas application of a single dose of the split vaccine was much less effective. Read More

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http://dx.doi.org/10.1134/S0006297920050041DOI Listing

In vitro Reconstitution of the S. aureus 30S Ribosomal Subunit and RbfA Factor Complex for Structural Studies.

Biochemistry (Mosc) 2020 May;85(5):545-552

Kazan Federal University, Kazan, 420008, Russia.

Ribosome-binding factor A (RbfA) from Staphylococcus aureus is a cold adaptation protein that is required for the growth of pathogenic cells at low temperatures (10-15°C). RbfA is involved in the processing of 16S rRNA, as well as in the assembly and stabilization of the small 30S ribosomal subunit. Structural studies of the 30S-RbfA complex will help to better understand their interaction, the mechanism of such complexes, and the fundamental process such as 30S subunit assembly that determines and controls the overall level of protein biosynthesis. Read More

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http://dx.doi.org/10.1134/S000629792005003XDOI Listing

Membrane Contacts in Plasmodesmata: Structural Components and Their Functions.

Biochemistry (Mosc) 2020 May;85(5):531-544

Lomonosov Moscow State University, Faculty of Biology, Department of Virology, Moscow, 119234, Russia.

Plasmodesmata (PD) are intercellular channels in plant tissues providing continuity of the cytoplasm, the plasma membrane (PM) and the endoplasmic reticulum (ER) of neighboring cells. These channels allow the active transport of macromolecules such as proteins or RNAs. Thus, PD are believed to play a critical role in the functional unity of plant tissues and the transport of signals required for plant development and responses to external stimuli. Read More

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http://dx.doi.org/10.1134/S0006297920050028DOI Listing

Molecular Targets in the Chemotherapy of Coronavirus Infection.

Authors:
O P Zhirnov

Biochemistry (Mosc) 2020 May;85(5):523-530

The Russian-German Academy of Medical and Biotechnological Sciences, Moscow, 121205, Skolkovo, Russia.

In the pathogenesis of the infectious process in the respiratory tract by SARS, MERS, and COVID-19 coronaviruses, two stages can be distinguished: early (etiotropic) and late (pathogenetic) ones. In the first stage, when the virus multiplication and accumulation are prevalent under insufficient host immune response, the use of chemotherapeutic agents blocking the reproduction of the virus is reasonable to suppress the development of the disease. This article considers six major chemotherapeutic classes aimed at certain viral targets: inhibitors of viral RNA polymerase, inhibitors of viral protease Mpro, inhibitors of proteolytic activation of viral protein S allowing virus entry into the target cell, inhibitors of virus uncoating in cellular endosomes, compounds of exogenous interferons, and compounds of natural and recombinant virus-neutralizing antibodies. Read More

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http://dx.doi.org/10.1134/S0006297920050016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232917PMC

Inorganic Polyphosphate and Physiological Properties of Saccharomyces cerevisiae Yeast Overexpressing Ppn2.

Biochemistry (Mosc) 2020 Apr;85(4):516-522

Pushchino Scientific Center for Biological Research, Skryabin Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia.

The effect of the yeast endopolyphosphatase Ppn2 overproduction on the metabolism of inorganic polyphosphates in Saccharomyces cerevisiae yeast was studied. Expression of the PPN2 gene under control of the strong constitutive promoter of glyceraldehyde 3-phosphate dehydrogenase gene (PKG1) led to a significant increase in the endopolyphosphatase activity stimulated by cobalt/zinc ions. This activity was present in both soluble and membrane subcellular fractions; it was higher toward long-chain polyphosphates and could be stimulated by ADP. Read More

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http://dx.doi.org/10.1134/S0006297920040124DOI Listing

Ouabain and Marinobufagenin: Physiological Effects on Human Epithelial and Endothelial Cells.

Biochemistry (Mosc) 2020 Apr;85(4):507-515

Lomonosov Moscow State University, Faculty of Biology, Moscow, 119234, Russia.

Long-term study on the identification of Na,K-ATPase endogenous inhibitors in mammalian tissues has resulted in the discovery of ouabain, marinobufagenin (MBG), and other cardiotonic steroids (CTS) in the blood plasma. Production of ouabain and MBG is increased in essential hypertension and other diseases associated with hypervolemia. Here, we compared the effects of ouabain and MBG on the Na,K-ATPase activity (measured as the transport of Na+, K+, and Rb ions) and proliferation and death of human renal epithelial cells (HRECs) and human umbilical vein endothelial cells (HUVEC) expressing α1-Na,K-ATPase. Read More

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http://dx.doi.org/10.1134/S0006297920040112DOI Listing

Structural Organization and Dynamic Characteristics of the Binding Site for Conformational Rearrangement Inhibitors in Hemagglutinins from H3N2 and H7N9 Influenza Viruses.

Biochemistry (Mosc) 2020 Apr;85(4):499-506

Lomonosov Moscow State University, Faculty of Bioengineering and Bioinformatics, Moscow, 119991, Russia.

Computer models of hemagglutinins from the H3N2 and H7N9 influenza viruses were developed to study structural organization and dynamic characteristics of the binding site for the conformational rearrangement inhibitors. The metadynamics was used to map the binding site free energy and to define the volume of its most energetically favorable states. It was demonstrated by simulation of the umifenovir (Arbidol) interaction with hemagglutinin that ligand binding requires an increase in the binding site volume and deformation of its most energetically favorable state. Read More

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http://dx.doi.org/10.1134/S0006297920040100DOI Listing

Analysis of Glycosyl-Enzyme Intermediate Formation in the Catalytic Mechanism of Influenza Virus Neuraminidase Using Molecular Modeling.

Biochemistry (Mosc) 2020 Apr;85(4):490-498

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119991, Russia.

Using classical molecular dynamics, constant-pH molecular dynamics simulation, metadynamics, and combined quantum mechanical and molecular mechanical approach, we identified an alternative pathway of glycosyl-enzyme intermediate formation during oligosaccharide substrate conversion by the influenza H5N1 neuraminidase. The Asp151 residue located in the enzyme mobile loop plays a key role in catalysis within a wide pH range due to the formation of a network of interactions with water molecules. Considering that propagation of influenza virus takes place in the digestive tract of birds at low pH values and in the human respiratory tract at pH values close to neutral, the existence of alternative reaction pathways functioning at different medium pH can explain the dual tropism of the virus and circulation of H5N1 viral strains capable of transmission from birds to humans. Read More

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http://dx.doi.org/10.1134/S0006297920040094DOI Listing

An Assay for the Activity of Base Excision Repair Enzymes in Cellular Extracts Using Fluorescent DNA Probes.

Biochemistry (Mosc) 2020 Apr;85(4):480-489

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russia.

Damaged DNA bases are removed by the base excision repair (BER) mechanism. This enzymatic process begins with the action of one of DNA glycosylases, which recognize damaged DNA bases and remove them by hydrolyzing N-glycosidic bonds with the formation of apurinic/apyrimidinic (AP) sites. Apurinic/apyrimidinic endonuclease 1 (APE1) hydrolyzes the phosphodiester bond on the 5'-side of the AP site with generation of the single-strand DNA break. Read More

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http://dx.doi.org/10.1134/S0006297920040082DOI Listing

High Level of Gene Transcription at the Embryonic Stage Leads to the Suppression of Heterochromatic Trans-Inactivation in Drosophila melanogaster Adults.

Biochemistry (Mosc) 2020 Apr;85(4):472-479

Institute of Molecular Genetics of the Russian Academy of Sciences, Moscow, 123182, Russia.

In some cases, gene transfer from euchromatin to constitutive heterochromatin as a result of chromosomal rearrangement is accompanied by epigenetic inactivation of this gene (cis-inactivation). In the case of trans-inactivation, transgenes in the normal chromosome are repressed by the cis-inactivation-causing rearranged homologous chromosome. Trans-inactivation is a result of the somatic pairing of homologs and the transfer of the normal chromosomal segment to the heterochromatic compartment of the nucleus. Read More

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http://dx.doi.org/10.1134/S0006297920040070DOI Listing

Substrate Diversity of L-Threonic Acid Dehydrogenase Homologs.

Biochemistry (Mosc) 2020 Apr;85(4):463-471

Guangdong Provincial Key Laboratory of Biotechnology for Plant Development, School of Life Sciences, South China Normal University, Guangzhou, Guangdong, 510631, China.

Despite physiological importance of aldonic sugar acids for living organisms, little is known about metabolic pathways of these compounds. Here, we investigated the functional diversity of homologs of L-threonic acid dehydrogenase (ThrDH; UniProt ID: Q0KBC7), an enzyme composed of two NAD-binding domains (PF14833 and PF03446). Ten ThrDH homologs with different genomic context were studied; seven new enzymatic activities were identified, such as (R)-pantoate dehydrogenase, L-altronic acid dehydrogenase, 6-deoxy-L-talonate dehydrogenase, L-idonic acid dehydrogenase, D-xylonic acid dehydrogenase, D-gluconic acid dehydrogenase, and 2-hydroxy-3-oxopantoate reductase activities. Read More

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http://dx.doi.org/10.1134/S0006297920040069DOI Listing

Protein Complex NDC80: Properties, Functions, and Possible Role in Pathophysiology of Cell Division.

Biochemistry (Mosc) 2020 Apr;85(4):448-462

Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, Moscow, 119991, Russia.

Mitotic division maintains genetic identity of any multicellular organism throughout an entire lifetime. Each time a parent cell divides, chromosomes are equally distributed between the daughter cells due to the action of mitotic spindle. Mitotic spindle is formed by the microtubules that represent dynamic polymers of tubulin protein. Read More

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http://dx.doi.org/10.1134/S0006297920040057DOI Listing

Mechanisms of TGFβ3 Action as a Therapeutic Agent for Promoting the Synthesis of Extracellular Matrix Proteins in Hyaline Cartilage.

Biochemistry (Mosc) 2020 Apr;85(4):436-447

Institute of Cytology, Russian Academy of Science, St. Petersburg, 194064, Russia.

Hyaline cartilage is a nonvascular connective tissue covering the joint surface. It consists mostly of the extracellular matrix proteins and a small number of highly differentiated chondrocytes. At present, various techniques for repairing joint surfaces damage, for example, the use of modified cell cultures and biodegradable scaffolds, are under investigation. Read More

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http://dx.doi.org/10.1134/S0006297920040045DOI Listing

Translesion DNA Synthesis and Carcinogenesis.

Biochemistry (Mosc) 2020 Apr;85(4):425-435

Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182, Russia.

Tens of thousands of DNA lesions are formed in mammalian cells each day. DNA translesion synthesis is the main mechanism of cell defense against unrepaired DNA lesions. DNA polymerases iota (Pol ι), eta (Pol η), kappa (Pol κ), and zeta (Pol ζ) have active sites that are less stringent toward the DNA template structure and efficiently incorporate nucleotides opposite DNA lesions. Read More

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http://dx.doi.org/10.1134/S0006297920040033DOI Listing

Catalytic Subunit of PKA as a Prototype of the Eukaryotic Protein Kinase Family.

Biochemistry (Mosc) 2020 Apr;85(4):409-424

Institute of Experimental Medicine, St. Petersburg, 197376, Russia.

The catalytic subunit of protein kinase A (PKAc) is conserved in all eukaryotic protein kinases. PKAc consists of two lobes that form the catalytic cleft containing the ATP-binding, peptide-binding site, and catalytic sites. During folding, PKAc secondary structures organize so that the non-polar regions form a globular core, while mobile loops and tails are exposed and can act as regulatory elements. Read More

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Amino Acids as Regulators of Cell Metabolism.

Biochemistry (Mosc) 2020 Apr;85(4):393-408

Institute of Cytochemistry and Molecular Pharmacology, Moscow, 115404, Russia.

In this review, we discuss the principles of regulation and synchronization of metabolic processes in mammalian cells using a two-component model of cell metabolism consisting of a controlling signaling system that regulates major enzymatic cascades and executive metabolic system that directly performs biosynthetic reactions. This approach has allowed us to distinguish two transitional metabolic states (from catabolism to anabolism and vice versa) accompanied by major rearrangements in the signaling system. The signaling system of natural amino acids was selected, because amino acids are involved in both signaling and executive metabolic subsystems of general cell metabolism. Read More

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http://dx.doi.org/10.1134/S000629792004001XDOI Listing

Unique Retinal Binding Pocket of Primate Blue-Sensitive Visual Pigment.

Biochemistry 2020 Jun 30. Epub 2020 Jun 30.

Department of Life Science and Applied Chemistry, Nagoya Institute of Technology, Showa-ku, Nagoya 466-8555, Japan.

The visual pigments of humans contain 11- retinal as the chromophore of light perception, and its photoisomerization to the all- form initiates visual excitation in our eyes. It is well-known that three isomeric states of retinal (11-, all-, and 9-) are in photoequilibrium at very low temperatures such as 77 K. Here we report the lack of formation of the 9- form in monkey blue (MB) at 77 K, as revealed by light-induced difference Fourier transform infrared spectroscopy. Read More

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http://dx.doi.org/10.1021/acs.biochem.0c00394DOI Listing

Cruciform DNA Sequences in Gene Promoters Can Impact Transcription upon Oxidative Modification of 2'-Deoxyguanosine.

Biochemistry 2020 Jun 25. Epub 2020 Jun 25.

Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah 84112-0850, United States.

Sequences of DNA typically adopt B-form duplexes in genomes, although noncanonical structures such as G-quadruplexes, i-motifs, Z-DNA, and cruciform structures can occur. A challenge is to determine the functions of these various structures in cellular processes. We and others have hypothesized that G-rich G-quadruplex-forming sequences in human genome promoters serve to sense oxidative damage generated during oxidative stress impacting gene regulation. Read More

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http://dx.doi.org/10.1021/acs.biochem.0c00387DOI Listing

Cytoskeletal Drugs Modulate Off-Target Protein Folding Landscapes Inside Cells.

Biochemistry 2020 Jun 28. Epub 2020 Jun 28.

The dynamic cytoskeletal network of microtubules and actin filaments can be disassembled by drugs. Cytoskeletal drugs work by perturbing the monomer-polymer equilibrium, thus changing the size and number of macromolecular crowders inside cells. Changes in both crowding and nonspecific surface interactions ("sticking") following cytoskeleton disassembly can affect the protein stability, structure, and function directly or indirectly by changing the fluidity of the cytoplasm and altering the crowding and sticking of other macromolecules in the cytoplasm. Read More

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http://dx.doi.org/10.1021/acs.biochem.0c00299DOI Listing