PDBsum entry: 1nwt

Signaling protein

PDB-id: 1nwt

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Description

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PROCHECK

Protein chains

362 a.a. *

Ligands

NAG-NAG ×4

NAG-NAG-NAG-NAG-NDG-NAG ×3

NDG-NAG-NAG-NDG-NAG

Waters ×470

* Residue conservation analysis

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Clefts Calculation

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PDB id:

1nwt

Name:

Signaling protein

Title:

Crystal structure of human cartilage gp39 (hc-gp39) in complex with chitopentaose

Structure:

Chitinase-3 like protein 1. Chain: a, b, c, d. Synonym: cartilage glycoprotein-39, gp-39, 39 kda synovial protein, ykl-40. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell: synovial cells, articular chondrocytes. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell: mammalian cho cells

UniProt:

Chains A, B, C, D: P36222 (CH3L1_HUMAN)

Seq:

Struc:

Seq:

383 a.a.

Struc:

362 a.a.

Key:	PfamA domain
Secondary structure	CATH domain

Resolution:

2.50Å

R-factor:

0.218

R-free:

0.253

Authors:

F.Fusetti,T.Pijning,K.H.Kalk,E.Bos,B.W.Dijkstra

Key ref:

F.Fusetti et al. (2003). Crystal structure and carbohydrate-binding properties of the human cartilage glycoprotein-39.. J Biol Chem, 278, 37753-37760. [PubMed id: 12851408] [DOI: 10.1074/jbc.M303137200]

Date:

06-Feb-03

Release date:

26-Aug-03

Related entries:

1nwr
crystal structure of human cartilage gp39 (hc-gp39)
1nws
crystal structure of human cartilage gp39 (hc-gp39) in
complex with chitobiose
1nwu
crystal structure of human cartilage gp39 (hc-gp39) in
complex with chitotetraose

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Surface

Key reference

DOI no: 10.1074/jbc.M303137200

J Biol Chem 278:37753-37760 (2003)

PubMed id: 12851408

Crystal structure and carbohydrate-binding properties of the human cartilage glycoprotein-39.

F.Fusetti, T.Pijning, K.H.Kalk, E.Bos, B.W.Dijkstra.

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.

Selected figure(s)

Figure 3.
FIG. 3. Model structure of HCgp-39 with a long chitin fragment. a, stereo view of the binding site showing the structure of a bound chitin oligosaccharide and the lining of aromatic amino acids. The "boat" structure of GlcNAc is visible in the -1 subsite. The F[o] -F[c] electron density map was calculated with the HCgp-39-(GlcNAc)[5] crystallographic data prior to model building of the ligand. (GlcNAc)[5] is shown in black in ball-and-stick representation; the HCgp-39 structure is shown as a ribbon representation in light gray. The aromatic residues lining the carbohydrate-binding site are shown in ball-and-stick representation. The figure was generated using the programs BOBSCRIPT (59) and RASTER-3D (58). b, schematic representation of the chitin-binding site showing protein-carbohydrate interactions at subsites -3 to +3, -6, and -5. The bound chitin and the amino acid side chains are shown in thick and thin black lines, respectively. The hydrogen-bonding interactions are shown as red dashed lines with atomic distances in Å. Amino acid residues having hydrophobic interactions with the bound chitin are schematically drawn as brown half-circles. Water molecules are shown as blue spheres. The figure was generated with the program LIGPLOT (60) followed by manual editing.

Figure 4.
FIG. 4. Surface representation of the structures of native HCgp-39 (a) and of HCgp-39 in complex with chito-oligosaccharides (b). The protein surface is colored as follows: aromatic amino acids are shown in cyan, Trp99 is depicted in violet, the putative heparin-binding site GRRDKQH (residues 143-149) is colored blue, and the epitope 259-271 is colored in red (residues 259-265) and orange (residues 266-271). The bound (GlcNAc)[5] and (GlcNAc)[2] are shown in white and pink sticks, respectively. The figure was generated with the program PyMOL (61).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 37753-37760) copyright 2003.

Figures were selected by the author.