title: Molecular dynamics simulations of a monofucosylated biantennary glycan of the N-acetyllactosamine type: the human lactotransferrin glycan.
abstract: Molecular dynamics simulations were carried out to explore the conformational flexibility of the antennae of N-linked glycans. They were performed over 200 ps in vacuo on the complete disialylated monofucosylated biantennary glycan of the N-acetyllactosaminic type. Starting from a bird-conformation, the 3-D-structure evolved through 9 successive transitional states to a new, compact and energetically favorable conformation which had never been previously described. In this conformation, both antennae are organized in two coplanar loops rolled in a contrary direction and oriented perpendicularly to the plane of the di-N-acetyl chitobiose residue leading to a 'lobster conformation'. All the glycosidic linkages of the disialylated monofucosylated biantennary glycan, except the Fuc(alpha 1-6)GlcNAc(beta 1-), were modified by a phase transition. Particularly, the Man(beta 1-4) GlcNAc(beta 1-) linkage, which was previously described by NMR and X-ray diffraction as a rigid one, was involved in numerous conformational changes during 83 ps, even before the first transition phase. The freedom of mobility of the torsional angles of the Man(alpha 1-6)Man(beta 1-) linkage was limited, under these simulation conditions, to the angle psi which took three values: 30 degrees, 90 degrees and 180 degrees. Moreover, from 150 ps up to the end of the simulation, the value of the torsional angle omega of the NeuAc(alpha 2-6)Gal(beta 1-) linkage of the alpha-1,6-antenna continuously swung between 60 degrees and -60 degrees. Finally, we observed that the values of the torsional angles of the three linkages: NeuAc(alpha 2-6)Gal(beta 1-), Gal(beta 1-4)GlcNAc(beta 1-) and GlcNAc(beta 1-2)Man(beta 1-) of each of the two antennae were different, demonstrating their asymmetric conformation.
authors.affiliation: Laboratoire de Génie Biologique et Médical, Unité INSERM U-279, Faculté de Pharmacie, Lille, France.
authors.forename: M
authors.initials: M
authors.lastname: Dauchez
authors.forename: J
authors.initials: J
authors.lastname: Mazurier
authors.forename: J
authors.initials: J
authors.lastname: Montreuil
authors.forename: G
authors.initials: G
authors.lastname: Spik
authors.forename: G
authors.initials: G
authors.lastname: Vergoten
mesh_terms: D000606:Amino Sugars / Q000737:chemistry; D002240:Carbohydrate Sequence; D006801:Humans; D007781:Lactoferrin / Q000737:chemistry*; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000737:chemistry*
chemical_list: D000606:Amino Sugars; D011134:Polysaccharides; C000458:N-acetyllactosamine; D007781:Lactoferrin