1HD4

SOLUTION STRUCTURE OF THE A-SUBUNIT OF HUMAN CHORIONIC GONADOTROPIN [MODELED WITH DIANTENNARY GLYCAN AT ASN78]

1HD4 の概要

• エントリーDOI: 10.2210/pdb1hd4/pdb
• 関連するPDBエントリー: 1DZ7 1E9J 1HCN 1HRP 1QFW 1XUL
• 分子名称: CHORIONIC GONADOTROPIN, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• 機能のキーワード: hcg, glycoprotein, chorionic gonadotropin, glycoprotein structure, xplor
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11859.26

構造登録者

Erbel, P.J.A.,Karimi-Nejad, Y.,van Kuik, J.A.,Boelens, R.,Kamerling, J.P.,Vliegenthart, J.F.G. (登録日: 2000-11-07, 公開日: 2000-12-07, 最終更新日: 2024-11-20)

主引用文献

Erbel, P.J.A.,Karimi-Nejad, Y.,van Kuik, J.A.,Boelens, R.,Kamerling, J.P.,Vliegenthart, J.F.G.
Effects of the N-Linked Glycans on the 3D Structure of the Free A-Subunit of Human Chorionic Gonadotropin
Biochemistry, 39:6012-6021, 2000

PubMed Abstract: To gain insight into intramolecular carbohydrate-protein interactions at the molecular level, the solution structure of differently deglycosylated variants of the alpha-subunit of human chorionic gonadotropin have been studied by NMR spectroscopy. Significant differences in chemical shifts and NOE intensities were observed for amino acid residues close to the carbohydrate chain at Asn78 upon deglycosylation beyond Asn78-bound GlcNAc. As no straightforward strategy is available for the calculation of the NMR structure of intact glycoproteins, a suitable computational protocol had to be developed. To this end, the X-PLOR carbohydrate force field designed for structure refinement was extended and modified. Furthermore, a computational strategy was devised to facilitate successful protein folding in the presence of extended glycans during the simulation. The values for phi and psi dihedral angles of the glycosidic linkages of the oligosaccharide core fragments GlcNAc2(beta1-4)GlcNAc1 and Man3(beta1-4)GlcNAc2 are restricted to a limited range of the broad conformational energy minima accessible for free glycans. This demonstrates that the protein core affects the dynamic behavior of the glycan at Asn78 by steric hindrance. Reciprocally, the NMR structures indicate that the glycan at Asn78 affects the stability of the protein core. The backbone angular order parameters and displacement data of the generated conformers display especially for the beta-turn 20-23 a decreased structural order upon splitting off the glycan beyond the Asn78-bound GlcNAc. In particular, the Asn-bound GlcNAc shields the protein surface from the hydrophilic environment through interaction with predominantly hydrophobic amino acid residues located in both twisted beta-hairpins consisting of residues 10-28 and 59-84.

PubMed: 10821673
DOI: 10.1021/BI992786N

実験手法

SOLUTION NMR