Unified picture for the conformation and stabilization of the O-glycosidic linkage in glycopeptide model structures

Pál D. Mezei, G. Csonka

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Glycoproteins play a central role in the immune response. In this study, we focus on the core of the common O-linked mucin-type glycopeptides. It has been observed that glycosylation stabilizes the protein in a stiffened, extended structure. We provide a unified picture for the conformation and stabilization of the O-glycosidic linkage using O-(2-acetylamino-2-deoxy-α- or -β-d-galacto- or -mannopyranosyl)-N-acetyl-l-serinamide model structures. We have calculated equilibrium geometries of the model structures with the B3LYP/6-31G(2df,p) method suggested in the Gaussian-4 theory. According to the relative energies, we confirm that the GalNAc-Ser linkage is more stable than its mannose analogues. The natural preference for the α-GalNAc-Ser over the β-GalNAc-Ser anomers can be explained by entropic effects. We explored the hydrogen bonding patterns on the carbohydrate unit calculating highly accurate dRPA@PBE0.25 and dRPA75 energies and found that in some cases, the acetamido group can be fixed by hydrogen bonding from the (O3Carb)H atom, but in most of the cases, it can rotate more freely. The torsion angles in the glycosidic linkage show that the linkage is stiffened more in the α-anomers and the most in the α-GalNAc-Ser structure because of the steric strains in the axial position and by two or three intramolecular hydrogen bonds. We also found that although, in our gas-phase model geometries, the peptide backbone prefers to be in a γ L-turn, a structural water molecule can stabilize a polyproline II helix of a proline-rich sequence, a β-sheet, or more likely random coils.

Original languageEnglish
Pages (from-to)1367-1376
Number of pages10
JournalStructural Chemistry
Volume26
Issue number5-6
DOIs
Publication statusPublished - Sep 4 2015

Fingerprint

Glycopeptides
Model structures
linkages
Conformations
Hydrogen bonds
Stabilization
stabilization
Glycosylation
Geometry
Mucins
Mannose
Proline
Torsional stress
Glycoproteins
carbohydrates
hydrogen
geometry
Gases
Carbohydrates
helices

Keywords

  • Density functional calculations
  • Glycopeptides
  • Glycoproteins
  • Glycosidic linkage

ASJC Scopus subject areas

  • Condensed Matter Physics
  • Physical and Theoretical Chemistry

Cite this

Unified picture for the conformation and stabilization of the O-glycosidic linkage in glycopeptide model structures. / Mezei, Pál D.; Csonka, G.

In: Structural Chemistry, Vol. 26, No. 5-6, 04.09.2015, p. 1367-1376.

Research output: Contribution to journalArticle

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