1nwt
From Proteopedia
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'''Crystal structure of human cartilage gp39 (HC-gp39) in complex with chitopentaose''' | '''Crystal structure of human cartilage gp39 (HC-gp39) in complex with chitopentaose''' | ||
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[[Category: Kalk, K H.]] | [[Category: Kalk, K H.]] | ||
[[Category: Pijning, T.]] | [[Category: Pijning, T.]] | ||
- | [[Category: | + | [[Category: Chitin]] |
- | [[Category: | + | [[Category: Chitinase-like protein]] |
- | [[Category: | + | [[Category: N-acetylglucosamine]] |
- | [[Category: | + | [[Category: Rheumatoid arthritis]] |
- | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 03:04:24 2008'' | |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + |
Revision as of 00:04, 3 May 2008
Crystal structure of human cartilage gp39 (HC-gp39) in complex with chitopentaose
Overview
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.
About this Structure
1NWT is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure and carbohydrate-binding properties of the human cartilage glycoprotein-39., Fusetti F, Pijning T, Kalk KH, Bos E, Dijkstra BW, J Biol Chem. 2003 Sep 26;278(39):37753-60. Epub 2003 Jul 8. PMID:12851408 Page seeded by OCA on Sat May 3 03:04:24 2008