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  • 1
    ISSN: 1573-5001
    Schlagwort(e): FKBP12 ; NMR detection ; sensitivity enhancement ; side chain–side chain hydrogen bonds
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract We describe the direct observation of side chain–side chain hydrogen bonding interactions in proteins with sensitivity-enhanced NMR spectroscopy. Specifically, the remote correlation between the guanidinium nitrogen 15Nε of arginine 71, which serves as the hydrogen donor, and the acceptor carboxylate carbon 13CO2 γ of aspartate 100 in a 12 kDa protein, human FKBP12, is detected via the trans-hydrogen bond 3h J Nε CO2γ coupling by employing a novel HNCO-type experiment, soft CPD-HNCO. The 3h J Nε CO2γ coupling constant appears to be even smaller than the average value of backbone 3h J NC′ couplings, consistent with more extensive local dynamics in protein side chains. The identification of trans-hydrogen bond J-couplings between protein side chains should provide useful markers for monitoring hydrogen bonding interactions that contribute to the stability of protein folds, to alignments within enzyme active sites and to recognition events at macromolecular interfaces.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    ISSN: 1573-5001
    Schlagwort(e): FKBP12 ; NMR detection ; sensitivity enhancement ; side chain–main chain hydrogen bonds
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract We describe the direct observation of very weak side chain–main chain hydrogen bonding interactions in medium-size 13C/15N-labeled proteins with sensitivity-enhanced NMR spectroscopy. Specifically, the remote correlation between the hydrogen acceptor side chain carboxylate carbon 13CO2 δ of glutamate 54 and the hydrogen donor backbone amide 15N of methionine 49 in a 12 kDa protein, human FKBP12, is detected via the trans-hydrogen bond 3h J NCO2δ coupling by employing a novel sensitivity-enhanced HNCO-type experiment, CPD-HNCO. The 3h J NCO2δ coupling constant appears to be even smaller than the average value of backbone 3h J NC′ couplings, consistent with more extensive local dynamics in protein side chains.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Weinheim : Wiley-Blackwell
    Angewandte Chemie International Edition in English 31 (1992), S. 384-400 
    ISSN: 0570-0833
    Schlagwort(e): Natural products ; Immunophilins ; Signal transduction ; Chemistry ; General Chemistry
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: One of the great mysteries of cell biology remains the mechanism of information transfer, or signaling, through the cytoplasm of the cell. Natural products that inhibit this process offer a unique window into fundamental aspects of cytoplasmic signal transduction, the means by which extracellular molecules influence intracellular events. Thus, natural products chemistry, including organic synthesis, conformational analysis, and methods of structure elucidation, is a powerful tool in the study of cell function. This article traces our understanding of a group of natural products from the finding that they inhibit cytoplasmic signaling to their current recognition as mediators of the interaction between widely distributed protein targets. The emphasis of the discussion is primarily structural. The interactions between the natural-product ligands and their protein receptors are analyzed at a molecular level in order to shed light on the molecular mechanisms of the biological functions of these compounds. In the process we hope to illustrate the power of chemical analysis as applied to biological systems. Through chemistry we can understand the molecular basis of biological phenomena.
    Zusätzliches Material: 16 Ill.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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