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    Wyświetlanie 1-3 z 3
    Tytuł:
    Hint2, the mitochondrial nucleoside 5-phosphoramidate hydrolase; properties of the homogeneous protein from sheep (Ovis aries) liver
    Autorzy:
    Bretes, Ewa
    Wojdyła-Mamoń, Anna
    Kowalska, Joanna
    Jemielity, Jacek
    Kaczmarek, Renata
    Baraniak, Janina
    Guranowski, Andrzej
    Powiązania:
    https://bibliotekanauki.pl/articles/1039587.pdf
    Data publikacji:
    2013
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    Hint1
    Hint2
    histidine triad nucleotide binding proteins
    purification to homogeneity
    nucleoside 5'-phosphoramidase
    Opis:
    Adenosine 5'-phosphoramidate (NH2-pA) is a rare natural nucleotide and its biochemistry and biological functions are poorly recognized. All organisms have proteins that may be involved in the catabolism of NH2-pA. They are members of the HIT protein family and catalyze hydrolytic splitting of NH2-pA to 5'-AMP and ammonia. At least five HIT proteins have been identified in mammals; however, the enzymatic and molecular properties of only Fhit and Hint1 have been comprehensively studied. Our study focuses on the Hint2 protein purified by a simple procedure to homogeneity from sheep liver mitochondrial fraction (OaHint2). Hint1 protein was also prepared from sheep liver (OaHint1) and the molecular and kinetic properties of the two proteins compared. Both function as homodimers and behave as nucleoside 5'-phosphoramidate hydrolases. The molecular mass of the OaHint2 monomer is 16 kDa and that of the OaHint1 monomer 14.9 kDa. Among potential substrates studied, NH2-pA appeared to be the best; the Km and kcat values estimated for this compound are 6.6 μM and 68.3 s-1, and 1.5 μM and 11.0 s-1 per natively functioning dimer of OaHint2 and OaHint1, respectively. Studies of the rates of hydrolysis of different NH2-pA derivatives show that Hint2 is more specific towards compounds with a P-N bond than Hint1. The thermostability of these two proteins is also compared.
    Źródło:
    Acta Biochimica Polonica; 2013, 60, 2; 249-254
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Tabubewältigung und Emotionen: Emotionsbasierte Implikaturen im Sprechakt der Andeutung
    Overcoming Verbal Taboos: E-Implicatures in Speech Act of Hinting
    Autorzy:
    Byelozyorova, Olena
    Powiązania:
    https://bibliotekanauki.pl/articles/458603.pdf
    Data publikacji:
    2020-06-20
    Wydawca:
    Uniwersytet Wrocławski. Oficyna Wydawnicza ATUT – Wrocławskie Wydawnictwo Oświatowe
    Tematy:
    implicature
    hint
    implicit speech act
    verbal taboo
    Opis:
    This paper deals with linguistic coping with verbal taboos through hints and focuses on e-implicatures and their triggers. These e-implicatures are based on emotional knowledge and give an affective judgement about the tabooed state-of-affairs. Emotions which evoke e-implicatures include disgust and fear and their tertiary dyad shame. Both verbal (euphemisms and aposiopesis) and non-verbal triggers (prosodic, kinetic and proxemics) ensure felicity of implying.
    Źródło:
    Linguistische Treffen in Wrocław; 2020, 17; 55-63
    2084-3062
    2657-5647
    Pojawia się w:
    Linguistische Treffen in Wrocław
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Pronukleotydy o strukturze amidofosforanów i ich wewnątrzkomórkowy mechanizm aktywacji
    Phosphoramidate pronucleotides and their intracellular activation mechanism
    Autorzy:
    Kulik, K.
    Baraniak, J.
    Powiązania:
    https://bibliotekanauki.pl/articles/171604.pdf
    Data publikacji:
    2014
    Wydawca:
    Polskie Towarzystwo Chemiczne
    Tematy:
    pronukleotydy
    amidofosforany
    aktywność fosforoamidazowa
    Hint
    białko triady histydynowej wiążącej nukleotyd
    prolek
    pronucleotides
    phosphoramidates
    phosphoramidase activity
    histidine triad nucleotide binding protein
    prodrug
    Opis:
    Nucleoside analogues have great therapeutic potential for the treatment of cancer and viral diseases. Once inside the cell, they are activated by a series of intracellular phosphorylation steps to produce 5’-triphosphate derivatives, which can be incorporated to DNA or RNA and act as terminators of growing polynucleotide chains [1c]. In many cases, nucleoside analogues are poor substrates for the cellular kinases needed for their activation [5]. It is clear that intracellular introduction of nucleoside analogues as phosphorylated metabolites (so called pronucleotides) could circumvent difficulties associated with the use of non-phosphorylated nucleoside analogues and could even activate inactive compounds or could increase the activity of the nucleoside analogues. However, polarity and a ready degradation by phosphatases make the use of free nucleotide analogues impractical. Therefore, much of the recent efforts have been focused on finding suitable prodrugs of nucleoside analogue monophosphates. Among the current diverse prodrug approaches, nucleoside phosphoramidate derivatives appear to be an interesting class of antiviral and anticancer agents [1c]. These prodrugs, as are devoid of negative charge, should be able to cross the cell membrane either by diffusion or utilizing transport protein [1c]. Conducted cell extract studies have provided evidence of a bioactivation mechanism that relies on enzyme-catalyzed P-N bond hydrolysis in phosphoramidate pronucleotides [1a,b]. It was assumed that phosphoramidate derivatives should generate nucleoside monophosphates inside the cell at rates that are influenced by both the nature of the amino group and the pH of the medium. Then nucleoside monophosphates should be phosphorylated in two different steps to the corresponding 5’-O-triphosphates (NTP) which can inhibit polymerase or be incorporated into the DNA strand being synthesized in the cell. Over the last decade extensive studies has been carried out to establish the mechanism of action of phosphoramidates and identification of enzymes responsible for bioactivation this pronucleotides to phosphorylated nucleosides [7, 21, 24]. Investigation of metabolism pathways provided evidence that phosphoramidase activity of Hint (histidine triad nucleotide-binding proteins) play a key role in the activation of phosphoramidate pronucleotides [23–27].
    Źródło:
    Wiadomości Chemiczne; 2014, 68, 9-10; 811-831
    0043-5104
    2300-0295
    Pojawia się w:
    Wiadomości Chemiczne
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
      Wyświetlanie 1-3 z 3

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