Chondroitin Sulfate-Specific Novel Hydrolase in Human

Conference paper
Part of the Advances in Experimental Medicine and Biology book series (volume 749)

Abstract

Chondroitin sulfate (CS) is widely distributed as the glycosaminoglycan side chains of proteoglycans in extracellular matrices and at the cell surface. CS chains have a linear structure composed of repeating disaccharide units comprising d-glucuronic acid and N-acetyl-d-galactosamine, which are sulfated at different positions in various combinations. This structural diversity is responsible for the multiple biological functions of CS.

The cellular degradation of CS occurs predominantly in lysosomes. Following the fragmentation of polysaccharides by endo-type hydrolases, the oligosaccharide products are degraded sequentially from the nonreducing end by exo-type glycosidases and sulfatases, although no endoglycosidases specific to CS have been reported. In this study, human hyaluronidase-4 was demonstrated to be a CS-specific endo-beta-N-acetylgalactosaminidase. The specificity of a purified recombinant form of the enzyme was investigated using various CS isoforms, and the structure of the best cleavage site was characterized.

This enzyme will be a useful tool for investigating CS-specific functions in tissues and cells without degrading hyaluronan. It may also be applicable to the treatment of acute spinal cord injuries instead of the bacterial CS lyase used in recent clinical trials.

Keywords

Sugar Migration Saccharide Hexa Polysaccharide 

Abbreviations

2AB

2-Aminobenzamide

Chn

Chondroitin

CS

Chondroitin sulfate

FITC

Fluorescein 5(6)-isothiocyanate

GalNAc

N-Acetyl-d-galactosamine

GlcNAc

N-Acetyl-d-glucosamine

GlcUA

d-Glucuronic acid

GPI

Glycosylphosphatidylinositol

HA

Hyaluronan

HPLC

High performance liquid chromatography

Notes

Acknowledgements

This work was supported in part by a Grant-in-aid for Scientific Research (C) (21590057) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT), and the Mizutani Foundation for Glycoscience, Tokyo, Japan. I thank Professor Kazuyuki Sugahara for his helpful suggestions as well as Tomoyuki Kneiwa, Anzu Miyazaki, and Shuji Mizumoto for their many contributions.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of PathobiochemistryFaculty of Pharmacy, Meijo UniversityNagoyaJapan

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