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

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Human YKL-39 is a pseudo-chitinase with retained chitooligosaccharide- binding properties. / Schimpl, Marianne; Rush, Christina L.; Betou, Marie; Eggleston, Ian M.; Recklies, Anneliese D.; van Aalten, Daan M. F. .

In: Biochemical Journal, Vol. 446, No. 1, 2012, p. 149-157.

Research output: Contribution to journalArticle

Harvard

Schimpl, M, Rush, CL, Betou, M, Eggleston, IM, Recklies, AD & van Aalten, DMF 2012, 'Human YKL-39 is a pseudo-chitinase with retained chitooligosaccharide- binding properties' Biochemical Journal, vol 446, no. 1, pp. 149-157.

APA

Schimpl, M., Rush, C. L., Betou, M., Eggleston, I. M., Recklies, A. D., & van Aalten, D. M. F. (2012). Human YKL-39 is a pseudo-chitinase with retained chitooligosaccharide- binding properties. Biochemical Journal, 446(1), 149-157doi: 10.1042/BJ20120377

Vancouver

Schimpl M, Rush CL, Betou M, Eggleston IM, Recklies AD, van Aalten DMF. Human YKL-39 is a pseudo-chitinase with retained chitooligosaccharide- binding properties. Biochemical Journal. 2012;446(1):149-157.

Author

Schimpl, Marianne; Rush, Christina L.; Betou, Marie; Eggleston, Ian M.; Recklies, Anneliese D.; van Aalten, Daan M. F. / Human YKL-39 is a pseudo-chitinase with retained chitooligosaccharide- binding properties.

In: Biochemical Journal, Vol. 446, No. 1, 2012, p. 149-157.

Research output: Contribution to journalArticle

Bibtex - Download

@article{7df761a20a09404b9341efc79d672f1d,
title = "Human YKL-39 is a pseudo-chitinase with retained chitooligosaccharide- binding properties",
author = "Marianne Schimpl and Rush, {Christina L.} and Marie Betou and Eggleston, {Ian M.} and Recklies, {Anneliese D.} and {van Aalten}, {Daan M. F.}",
year = "2012",
volume = "446",
number = "1",
pages = "149--157",
journal = "Biochemical Journal",
issn = "0264-6021",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Human YKL-39 is a pseudo-chitinase with retained chitooligosaccharide- binding properties

A1 - Schimpl,Marianne

A1 - Rush,Christina L.

A1 - Betou,Marie

A1 - Eggleston,Ian M.

A1 - Recklies,Anneliese D.

A1 - van Aalten,Daan M. F.

AU - Schimpl,Marianne

AU - Rush,Christina L.

AU - Betou,Marie

AU - Eggleston,Ian M.

AU - Recklies,Anneliese D.

AU - van Aalten,Daan M. F.

PY - 2012

Y1 - 2012

N2 - 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. © 2012 The Author(s).

AB - 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. © 2012 The Author(s).

UR - http://www.scopus.com/inward/record.url?partnerID=yv4JPVwI&eid=2-s2.0-84864743661&md5=18079b324a96f66c00a6dfb17f1c3fc5

U2 - 10.1042/BJ20120377

DO - 10.1042/BJ20120377

M1 - Article

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 1

VL - 446

SP - 149

EP - 157

ER -

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