X-ray crystal structures of rabbit N-acetylglucosaminyltransferase I (GnT I) in complex with donor substrate analogues
| Autor: | Stephen G. Withers, Roni D. Gordon, Malathy Satkunarajah, Dengbo Ma, Prashanth Sivarajah, Dragos Vizitiu, James M. Rini, Chris A. Tarling |
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| Rok vydání: | 2006 |
| Předmět: |
Models
Molecular Stereochemistry Protein Data Bank (RCSB PDB) Oligosaccharides Crystallography X-Ray N-Acetylglucosaminyltransferases Catalysis Substrate Specificity chemistry.chemical_compound Structural Biology Glycosyltransferase Transferase Moiety Molecule Animals Molecular Biology biology Chemistry Substrate (chemistry) Glycosyltransferases Acceptor Phosphonate Protein Structure Tertiary carbohydrates (lipids) Crystallography Kinetics Models Chemical biology.protein Rabbits Mannose Protein Binding |
| Zdroj: | Journal of molecular biology. 360(1) |
| ISSN: | 0022-2836 |
| Popis: | The Golgi-resident glycosyltransferase, UDP-N-acetyl-d-glucosamine:alpha-3-d-mannoside beta-1,2-N-acetylglucosaminyltransferase I (GnT I), initiates the conversion of high-mannose oligosaccharides to complex and hybrid structures in the biosynthesis of N-linked glycans. Reported here are the X-ray crystal structures of GnT I in complex with UDP-CH2-GlcNAc (a non-hydrolyzable C-glycosidic phosphonate), UDP-2-deoxy-2-fluoro-glucose, UDP-glucose and UDP. Collectively, these structures provide evidence for the importance of the GlcNAc moiety and its N-acetyl group in donor substrate binding, as well as insight into the role played by the flexible 318-330 loop in substrate binding and product release. In addition, the UDP-CH2-GlcNAc complex reveals a well-defined glycerol molecule poised for nucleophilic attack on the C1 atom of the donor substrate analogue. The position and orientation of this glycerol molecule have allowed us to model the binding of the Manalpha1,3Manbeta1 moiety of the acceptor substrate and, based on the model, to suggest a rationalization for the main determinants of GnT I acceptor specificity. |
| Databáze: | OpenAIRE |
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