Document Detail


Human YKL-39 is a pseudo-chitinase with retained chitooligosaccharide-binding properties.
MedLine Citation:
PMID:  22742450     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Marianne Schimpl; Christina L Rush; Marie Betou; Ian M Eggleston; Anneliese D Recklies; Daan M F van Aalten
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  446     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-07-27     Completed Date:  2012-10-29     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  149-57     Citation Subset:  IM    
Affiliation:
Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK.
Data Bank Information
Bank Name/Acc. No.:
PDB/4AY1
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MeSH Terms
Descriptor/Qualifier:
Acetylglucosamine / metabolism
Adipokines / antagonists & inhibitors,  chemistry*,  genetics,  metabolism*
Amino Acid Substitution
Catalytic Domain
Chitin / metabolism
Chitinase / chemistry,  metabolism
Crystallography, X-Ray
Enzyme Inhibitors / chemistry,  pharmacology
Humans
Lectins / antagonists & inhibitors,  chemistry*,  genetics,  metabolism*
Oligosaccharides / chemistry,  metabolism
Point Mutation
Protein Conformation
Protein Folding
Tryptophan / metabolism
Grant Support
ID/Acronym/Agency:
087590//Wellcome Trust; G0900138//Medical Research Council; G0900138(90614)//Medical Research Council; //Wellcome Trust
Chemical
Reg. No./Substance:
0/Adipokines; 0/CHI3L1 protein, human; 0/Enzyme Inhibitors; 0/Lectins; 0/Oligosaccharides; 1398-61-4/Chitin; 73-22-3/Tryptophan; 7512-17-6/Acetylglucosamine; EC 3.2.1.14/Chitinase
Comments/Corrections

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