Projects per year
Abstract
The chitinase-like proteins YKL-39 (chitinase 3-like-2) and YKL-40 (chitinase 3-like-1) are highly expressed in a number of human cells independent of their origin (mesenchymal, epithelial or haemapoietic). Elevated serum levels of YKL-40 have been associated with a negative outcome in a number of diseases ranging from cancer to inflammation and asthma. YKL-39 expression has been associated with osteoarthritis. However, despite the reported association with disease, the physiological or pathological role of these proteins is still very poorly understood. Although YKL-39 is homologous to the two family 18 chitinases in the human genome, it has been reported to lack any chitinase activity. In the present study, we show that human YKL-39 possesses a chitinase-like fold, but lacks key active-site residues required for catalysis. A glycan screen identified oligomers of N-acetylglucosamine as preferred binding partners. YKL-39 binds chitooligosaccharides and a newly synthesized derivative of the bisdionin chitinase-inhibitor class with micromolar affinity, through a number of conserved tryptophan residues. Strikingly, the chitinase activity of YKL-39 was recovered by reverting two non-conservative substitutions in the active site to those found in the active enzymes, suggesting that YKL-39 is a pseudo-chitinase with retention of chitinase-like ligand-binding properties.
Original language | English |
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Pages (from-to) | 149-157 |
Number of pages | 9 |
Journal | Biochemical Journal |
Volume | 446 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2012 |
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Dive into the research topics of 'Human YKL-39 is a pseudo-chitinase with retained chitooligosaccharide- binding properties'. Together they form a unique fingerprint.Projects
- 2 Finished
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Aref#d: 21559. Molecular Mechanisms of Fungal Cell Wall Assembly (Programme Grant)
van Aalten, D. (Investigator)
1/11/09 → 31/10/14
Project: Research
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Aref#d: 21318. Molecular Mechanisms of O-GlcNAc Signalling (Senior Fellowship Renewal)
van Aalten, D. (Investigator)
1/06/09 → 29/02/16
Project: Research