| |  Online-Ressource |
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| Verfasst von: | Persch, Elke [VerfasserIn]  |
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| | Bryson, Steve [VerfasserIn] |
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| | Todoroff, Nickolay K. [VerfasserIn] |
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| | Eberle, Christian [VerfasserIn] |
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| | Thelemann, Jonas [VerfasserIn] |
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| | Dirdjaja, Natalie [VerfasserIn] |
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| | Kaiser, Marcel [VerfasserIn] |
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| | Weber, Maria [VerfasserIn] |
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| | Derbani, Hassan [VerfasserIn] |
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| | Brun, Reto [VerfasserIn] |
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| | Schneider, Gisbert [VerfasserIn] |
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| | Pai, Emil F. [VerfasserIn] |
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| | Krauth-Siegel, Renate [VerfasserIn] |
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| | Diederich, François [VerfasserIn] |
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| Titel: | Binding to large enzyme pockets |
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| Titelzusatz: | small-molecule inhibitors of trypanothione reductase |
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| Verf.angabe: | Elke Persch, Steve Bryson, Nickolay K. Todoroff, Christian Eberle, Jonas Thelemann, Natalie Dirdjaja, Marcel Kaiser, Maria Weber, Hassan Derbani, Reto Brun, Gisbert Schneider, Emil F. Pai, R. Luise Krauth-Siegel, and François Diederich |
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| E-Jahr: | 2014 |
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| Jahr: | April 30, 2014 |
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| Umfang: | 12 S. |
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| Fussnoten: | Gesehen am 01.09.2020 |
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| Titel Quelle: | Enthalten in: ChemMedChem |
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| Ort Quelle: | Weinheim [u.a.] : Wiley-VCH, 2006 |
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| Jahr Quelle: | 2014 |
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| Band/Heft Quelle: | 9(2014), 8, Seite 1880-1891 |
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| ISSN Quelle: | 1860-7187 |
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| Abstract: | Abstract The causative agents of the parasitic disease human African trypanosomiasis belong to the family of trypanosomatids. These parasitic protozoa exhibit a unique thiol redox metabolism that is based on the flavoenzyme trypanothione reductase (TR). TR was identified as a potential drug target and features a large active site that allows a multitude of possible ligand orientations, which renders rational structure-based inhibitor design highly challenging. Herein we describe the synthesis, binding properties, and kinetic analysis of a new series of small-molecule inhibitors of TR. The conjunction of biological activities, mutation studies, and virtual ligand docking simulations led to the prediction of a binding mode that was confirmed by crystal structure analysis. The crystal structures revealed that the ligands bind to the hydrophobic wall of the so-called ?mepacrine binding site?. The binding conformation and potency of the inhibitors varied for TR from Trypanosoma brucei and T.?cruzi. |
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| DOI: | doi:10.1002/cmdc.201402032 |
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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: https://doi.org/10.1002/cmdc.201402032 |
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| | Volltext: https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/cmdc.201402032 |
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| | DOI: https://doi.org/10.1002/cmdc.201402032 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | docking |
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| | inhibitors |
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| | mutation studies |
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| | structure-based design |
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| | trypanothione reductases |
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| | X-ray structures |
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| K10plus-PPN: | 1728365406 |
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| Verknüpfungen: | → Zeitschrift |
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Binding to large enzyme pockets / Persch, Elke [VerfasserIn]; April 30, 2014 (Online-Ressource)
