| DOI | Trouver le DOI : https://doi.org/10.1007/s10719-012-9411-4 |
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| Auteur | Rechercher : Landström, Jens; Rechercher : Persson, Karina; Rechercher : Rademacher, Christoph; Rechercher : Lundborg, Magnus; Rechercher : Wakarchuk, Warren1; Rechercher : Peters, Thomas; Rechercher : Widmalm, Göran |
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| Affiliation | - Conseil national de recherches du Canada. Thérapeutique en santé humaine
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| Format | Texte, Article |
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| Sujet | glycosyltransferase; inhibitor; NMR; molecular modeling; screening |
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| Résumé | The α-1,3-glucosyltransferase WaaG is involved in the synthesis of the core region of lipopolysaccharides in E. coli. A fragment-based screening for inhibitors of the WaaG glycosyltrasferase donor site has been performed using NMR spectroscopy. Docking simulations were performed for three of the compounds of the fragment library that had shown binding activity towards WaaG and yielded 3D models for the respective complexes. The three ligands share a hetero-bicyclic ring system as a common structural motif and they compete with UDP-Glc for binding. Interestingly, one of the compounds promoted binding of uridine to WaaG, as seen from STD NMR titrations, suggesting a different binding mode for this ligand. We propose these compounds as scaffolds for the design of selective high-affinity inhibitors of WaaG. Binding of natural substrates, enzymatic activity and donor substrate selectivity were also investigated by NMR spectroscopy. Molecular dynamics simulations of WaaG were carried out with and without bound UDP and revealed structural changes compared to the crystal structure and also variations in flexibility for some amino acid residues between the two WaaG systems studied. |
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| Date de publication | 2012-06-19 |
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| Dans | |
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| Langue | anglais |
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| Publications évaluées par des pairs | Oui |
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| Identificateur | 9411 |
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| Numéro NPARC | 21268380 |
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| Exporter la notice | Exporter en format RIS |
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| Signaler une correction | Signaler une correction (s'ouvre dans un nouvel onglet) |
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| Identificateur de l’enregistrement | 0f08e56f-847a-46e3-90b0-5c5469a5693b |
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| Enregistrement créé | 2013-07-08 |
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| Enregistrement modifié | 2020-04-21 |
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