Human YKL-39 is a pseudo-chitinase with retained chitooligosaccharide-binding properties
Schimpl, M., Rush, C. l., Betou, M., Eggleston, I. M., Recklies, A. d. and Van aalten, D. m. F., 2012. Human YKL-39 is a pseudo-chitinase with retained chitooligosaccharide-binding properties. Biochemical Journal, 446 (1), pp. 149-157.
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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.
|Creators||Schimpl, M., Rush, C. l., Betou, M., Eggleston, I. M., Recklies, A. d. and Van aalten, D. m. F.|
|Departments||Faculty of Science > Pharmacy & Pharmacology|
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