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| Verfasst von: | Peters, Verena [VerfasserIn]  |
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| | Schmitt, Claus P. [VerfasserIn] |
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| | Weigand, Tim [VerfasserIn] |
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| | Klingbeil, Kristina [VerfasserIn] |
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| | Thiel, Christian [VerfasserIn] |
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| | Berg, Antje van den [VerfasserIn] |
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| | Nawroth, Peter Paul [VerfasserIn] |
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| | Fleming, Thomas [VerfasserIn] |
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| | Wagner, Andreas H. [VerfasserIn] |
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| | Hecker, Markus [VerfasserIn] |
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| Titel: | Allosteric inhibition of carnosinase (CN1) by inducing a conformational shift |
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| Verf.angabe: | Verena Peters, Claus P. Schmitt, Tim Weigand, Kristina Klingbeil, Christian Thiel, Antje van den Berg, Vittorio Calabrese, Peter Nawroth, Thomas Fleming, Elisabete Forsberg, Andreas H. Wagner, Markus Hecker, & Giulio Vistoli |
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| E-Jahr: | 2017 |
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| Jahr: | 04 Aug 2017 |
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| Umfang: | 9 S. |
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| Fussnoten: | Gesehen am 01.08.2018 |
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| Titel Quelle: | Enthalten in: Journal of enzyme inhibition and medicinal chemistry |
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| Ort Quelle: | Abingdon : Taylor & Francis Group, 1985 |
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| Jahr Quelle: | 2017 |
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| Band/Heft Quelle: | 32(2017), 1, Seite 1102-1110 |
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| ISSN Quelle: | 1475-6374 |
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| Abstract: | In humans, low serum carnosinase (CN1) activity protects patients with type 2 diabetes from diabetic nephropathy. We now characterized the interaction of thiol-containing compounds with CN1 cysteine residue at position 102, which is important for CN1 activity. Reduced glutathione (GSH), N-acetylcysteine and cysteine (3.2 ± 0.4, 2.0 ± 0.3, 1.6 ± 0.2 µmol/mg/h/mM; p < .05) lowered dose-dependently recombinant CN1 (rCN1) efficiency (5.2 ± 0.2 µmol/mg/h/mM) and normalized increased CN1 activity renal tissue samples of diabetic mice. Inhibition was allosteric. Substitution of rCN1 cysteine residues at position 102 (Mut1C102S) and 229 (Mut2C229S) revealed that only cysteine-102 is influenced by cysteinylation. Molecular dynamic simulation confirmed a conformational rearrangement of negatively charged residues surrounding the zinc ions causing a partial shift of the carnosine ammonium head and resulting in a less effective pose of the substrate within the catalytic cavity and decreased activity. Cysteine-compounds influence the dynamic behaviour of CN1 and therefore present a promising option for the treatment of diabetes. |
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| DOI: | doi:10.1080/14756366.2017.1355793 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: http://dx.doi.org/10.1080/14756366.2017.1355793 |
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| | Volltext: https://doi.org/10.1080/14756366.2017.1355793 |
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| | DOI: https://doi.org/10.1080/14756366.2017.1355793 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | allosteric inhibition |
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| | Carnosinase 1 activity |
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| | CN1 |
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| | diabetes |
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| | glutathione |
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| | N-acetylcysteine |
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| K10plus-PPN: | 1578173914 |
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| Verknüpfungen: | → Zeitschrift |
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Allosteric inhibition of carnosinase (CN1) by inducing a conformational shift / Peters, Verena [VerfasserIn]; 04 Aug 2017 (Online-Ressource)
