Human YKL-39 is a pseudo-chitinase with retained chitooligosaccharide- binding properties

Marianne Schimpl, Christina L. Rush, Marie Betou, Ian M. Eggleston, Anneliese D. Recklies, Daan M. F. van Aalten

    Research output: Contribution to journalArticlepeer-review

    57 Citations (Scopus)

    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 languageEnglish
    Pages (from-to)149-157
    Number of pages9
    JournalBiochemical Journal
    Volume446
    Issue number1
    DOIs
    Publication statusPublished - 2012

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