Stereochemistry of the N-glycosylation sites in glycoproteins.
The stereochemical features displayed by the N-glycosidic linkage in crystalline N-linked glycoproteins are analyzed. From the statistical analysis of 44 different glycosylation sites belonging to 26 glycoproteins of the Brookhaven Protein Data Bank, a mean standard geometry for the GlcNAc moiety, along with a rationalization of its conformational behavior, can be proposed. As for the glycopeptide linkage, the distribution of observed conformations has been analyzed on the basis of molecular mechanics calculations. The rotamer distribution of the Asn side chains conforms to that observed on non-glycosylated structures, and it agrees with the pattern of flexible conformations gathered from NMR measurements. In characterizing the protein-glycan interactions, some hydrogen bonds occur. Stacking between the amphiphilic moiety of the glycan and some surrounding aromatic, or at least hydrophobic, amino acid residues is also found. When looking at the secondary structure of the glycosylated peptide, only 25% of the glycosylation sites correspond to situations where Asn is located at the top of a beta-turn. Other types of secondary structure exist which fulfill the spatial requirement of having the glycan exposed at the surface of the protein. These data can be compared with the most recent studies on the peptide conformation which would be required for glycosylation.
Imberty
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Laboratorie de Synthèse Organique-CNRS Faculté des Sciences et Techniques, Nantes, France.
Pérez
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D000596:Amino Acids / Q000737:chemistry; D006020:Glycopeptides / Q000737:chemistry; D006023:Glycoproteins / Q000737:chemistry*; D006031:Glycosylation; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D017433:Protein Structure, Secondary
D000596:Amino Acids; D006020:Glycopeptides; D006023:Glycoproteins