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Small molecules con...
Small molecules containing hetero-bicyclic ring systems compete with UDP-Glc for binding to WaaG glycosyltransferase
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- Landström, Jens (författare)
- Stockholms universitet,Institutionen för organisk kemi,Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University,Göran Widmalm
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- Persson, Karina, 1969- (författare)
- Umeå universitet,Kemiska institutionen,Karina Persson
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- Rademacher, Christoph (författare)
- Institute of Chemistry, University of Luebeck,Thomas Peters
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- Lundborg, Magnus (författare)
- Stockholms universitet,Institutionen för organisk kemi,Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University,Göran Widmalm
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- Wakarchuk, Warren (författare)
- National Research Council of Canada,Warren Wakarchuk
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- Thomas, Peters (författare)
- Institute of Chemistry, University of Luebeck,Thomas Peters
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- Widmalm, Göran (författare)
- Stockholms universitet,Institutionen för organisk kemi,Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University,Göran Widmalm
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(creator_code:org_t)
- 2012-06-19
- 2012
- Engelska.
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Ingår i: Glycoconjugate Journal. - : Springer. - 0282-0080 .- 1573-4986. ; 29:7, s. 491-502
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- NATURVETENSKAP -- Kemi -- Organisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Organic Chemistry (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- Glycosyltransferase
- Inhibitor
- NMR
- Molecular modeling
- Screening
- organisk kemi
- Organic Chemistry
- biologisk kemi
- biological chemistry
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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