Heparan sulfate 6-O-sulfotransferase

Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for... – Transferase other than ribonuclease

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435 84, 435101, 435130, 435183, C12N 910, C12P 1926

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active

058342826

ABSTRACT:
The present invention provides a heparan sulfate 6-O-sulfotransferase for selectively introducing sulfate group into hydroxyl group at C-6 of glucosamine of heparin and heparan sulfate, having the following properties: (i) sulfate group is selectively transferred from a sulfate group donor to hydroxyl group at C-6 of N-sulfoglucosamine residue; (ii) sulfate group is transferred to CDSNS-heparan, but sulfate group is not transferred to chondroitin and chondroitin-4-sulfate; (iii) optimum reaction pH is in a range of pH 6-7; (iv) optimum ionic strength is in a range of 0.1-0.3 M (in the case of sodium chloride); and (v) the enzyme activity is inhibited by dithiothreitol and adenosine-3',5'-diphosphate, and activated by protamine.

REFERENCES:
I. Jacobsson et al., "Biosynthesis of Heparin", The Journal of Biological Chemistry, Jun. 1980, vol. 255, No. 11, pp. 5094-5100.
D. Gohler et al., "Purification and Characterization of 3'--phosphoadenylylsulfate: N-desulfoheparan sulfate sulfotransferase from arterial tissue" European Journal of Biochemistry, vol. 138, 1984, pp. 301-308.
H. Inoue et al., "Glycosaminoglycan Sulfotransferases in Human and Animal Sera", The Journal of Biological Chemistry, Apr. 1986, vol. 261, No. 10, pp. 4460-4469.
E. Brandan et al., "Purification of Rat Liver N-Heparan-sulfate Sulfotransferase", The Journal of Biological Chemistry, Feb. 1988, vol. 263, No. 5, pp. 2417-2422.
M. Kusche et al., "Biosynthesis of Heparin; O-Sulfation of the Antithrombin-Binding Region", The Journal of Biological Chemistry, Oct. 1988, vol. 263, No. 30, pp. 15474-15484.
M. Kushce et al., "Biosynthesis of Heparin; O-Sulfation of D-Glucuronic Acid Units", The Journal of Biological Chemistry, Sep. 1990, vol. 265, No. 26, pp. 15403-15409.
Translation of "Sulfotransferases in Tissues" in Shin-Seikagaku-Jikken-Koza, 3, p. 194, published by Tokyo-Kagaku-Dojin, Apr. 1991.
M. Kushce et al., "Biosynthesis of Heparin; Enzymatic Sulfation of Pentasaccharides", The Journal of Biological Chemistry, Apr. 1991, vol. 266, No. 12, pp. 7400-7409.
I. Pettersson et al., "Biosynthesis of Heparin; Purification of A 110-kDa Mouse Mastocytoma Protein Required for Both Glucosaminyl N-Deacetylation and N-Sulfation", The Journal of Biological Chemistry, May 1991, vol. 266, No. 13, pp. 8044-8049.
H. Wlad et al., "Partial Purification of O-Sulfotransferases Involved in the Biosynthesis of Heparin", Glycoconjugate Journal, 1991 vol. 8, pp. 200-201.
Translation of "Isolating and Refining the Heparan Sulfate 6-Sulfated Enzyme" The Journal of Biochemistry issued by Japanese Biochemical Society, vol. 66, No. 7, 1994, p. 1043.
H. Wlad et al., "Biosynthesis of Heparin; Different Molecular Forms of O-Sulfotransferases", The Journal of Biological Chemistry, Oct. 1994, vol. 269, No. 40, pp. 24538-24541.
H. Habuchi et al., "Purification and Characterization of Heparan Sulfate 6-Sulfotransferase from the Culture Medium of Chinese Hamster Overy Cells", The Journal of Biological Chemistry, Feb. 1995, vol. 270, No. 8, pp. 4172-4179.
Hanna Wlad et al., "Partial Purification of O-Sulfotransferases Involved in the Biosynthesis of Heparin", Glycoconjugate Journal, pp. 200-201, vol. 8, No. 3, Jun. 1991.
Hanna Wlad et al., "Biosynthesis of Heparin", Journal of Biological Chemistry, pp. 24538-24541, vol. 269, No. 40, Oct. 1994.
Hiroko Habuchi et al., "Purification and Characterization of Heparan Sulfate 6-Sulfotransferase from the Culture Medium of Chinese Hamster Ovary Cells", Journal of Biological Chemistry, pp. 4172-4179, vol. 270, No. 8, Feb. 1995.

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