4AY1

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

Summary for 4AY1

• Entry DOI: 10.2210/pdb4ay1/pdb
• Descriptor: CHITINASE-3-LIKE PROTEIN 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: chilectin, lectin, chitooligosaccharide, pseudochitinase, hydrolase
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 12
• Total formula weight: 501819.85

Authors

Schimpl, M.,Rush, C.L.,Betou, M.,Eggleston, I.M.,Penman, G.A.,Recklies, A.D.,van Aalten, D.M.F. (deposition date: 2012-06-17, release date: 2012-08-08, Last modification date: 2024-10-23)

Primary citation

Schimpl, M.,Rush, C.L.,Betou, M.,Eggleston, I.M.,Recklies, A.D.,Van Aalten, D.M.F.
Human Ykl-39 is a Pseudo-Chitinase with Retained Chitooligosaccharide-Binding Properties.
Biochem.J., 446:149-, 2012

PubMed 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.

PubMed: 22742450
DOI: 10.1042/BJ20120377

Experimental method

X-RAY DIFFRACTION (1.95 Å)