1NWU

Crystal structure of human cartilage gp39 (HC-gp39) in complex with chitotetraose

1NWU の概要

• エントリーDOI: 10.2210/pdb1nwu/pdb
• 関連するPDBエントリー: 1nwr 1nws 1nwt
• 分子名称: Chitinase-3 like protein 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-alpha-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: chitinase-like protein, rheumatoid arthritis, chitin, n-acetylglucosamine, signaling protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 167167.78

構造登録者

Fusetti, F.,Pijning, T.,Kalk, K.H.,Bos, E.,Dijkstra, B.W. (登録日: 2003-02-06, 公開日: 2003-08-26, 最終更新日: 2024-11-06)

主引用文献

Fusetti, F.,Pijning, T.,Kalk, K.H.,Bos, E.,Dijkstra, B.W.
Crystal structure and carbohydrate-binding properties of the human cartilage glycoprotein-39
J.Biol.Chem., 278:37753-37760, 2003

PubMed Abstract: The human cartilage glycoprotein-39 (HCgp-39 or YKL40) is expressed by synovial cells and macrophages during inflammation. Its precise physiological role is unknown. However, it has been proposed that HCgp-39 acts as an autoantigen in rheumatoid arthritis, and high expression levels have been associated with cancer development. HCgp-39 shares high sequence homology with family 18 chitinases, and although it binds to chitin it lacks enzymatic activity. The crystal structure of HCgp-39 shows that the protein displays a (beta/alpha)8-barrel fold with an insertion of an alpha + beta domain. A 43-A long carbohydrate-binding cleft is present at the C-terminal side of the beta-strands in the (beta/alpha)8 barrel. Binding of chitin fragments of different lengths identified nine sugar-binding subsites in the groove. Protein-carbohydrate interactions are mainly mediated by stacking of side chains of aromatic amino acid residues. Surprisingly, the specificity of chitin binding to HCgp-39 depends on the length of the oligosaccharide. Although chitin disaccharides tend to occupy the distal subsites, longer chains bind preferably to the central subsites in the groove. Despite the absence of enzymatic activity, long chitin fragments are distorted upon binding, with the GlcNAc at subsite -1 in a boat conformation, similar to what has been observed in chitinases. The presence of chitin in the human body has never been documented so far. However, the binding features observed in the complex structures suggest that either chitin or a closely related oligosaccharide could act as the physiological ligand for HCgp-39.

PubMed: 12851408
DOI: 10.1074/jbc.M303137200

実験手法

X-RAY DIFFRACTION (2.2 Å)