![]()
|
|
||||||||
J Biol Chem, Vol. 274, Issue 5, 2690-2695, January 29, 1999
From the Division of Cellular and Molecular Medicine, Glycobiology
Program, University of California, San Diego,
La Jolla, California 92093-0687
N-Deacetylation and
N-sulfation of N-acetylglucosamine residues in
heparan sulfate and heparin initiate a series of chemical modifications
that ultimately lead to oligosaccharide sequences with specific ligand
binding properties. These reactions are catalyzed by GlcNAc
N-deacetylase/N-sulfotransferase (NDST), a
monomeric enzyme with two catalytic activities. Two genes encoding NDST isozymes have been described, one from rat liver (NDST1) and another from murine mastocytoma (NDST2). Both isozymes are expressed in tissues
in varying amounts, but their relative contribution to heparan sulfate
formation in any one tissue is unknown. We now report the
identification of a third member of the NDST family, designated NDST3.
A full-length cDNA clone (3.2 kilobase pairs) encoding a 873-amino
acid protein was obtained from a human fetal/infant brain cDNA
library. Human NDST3 (hNDST3) has a nucleotide sequence homologous but
not identical to hNDST1 and NDST2. The deduced amino acid sequence
shows 70% and 65% amino acid identity to that of hNDST1 and NDST2,
respectively. A soluble chimera of hNDST3 and protein A exhibited both
N-deacetylase and N-sulfotransferase activity,
confirming its enzymatic identity. Northern blot analysis of human
fetal brain poly(A)+ RNA showed a single transcript of 6.4 kilobase pairs. Reverse transcription polymerase chain reaction
analysis revealed more restricted tissue expression of hNDST3 than
hNDST1 and NDST2, and high levels in brain, liver, and kidney. Analysis
of Chinese hamster ovary cells revealed expression of NDST1 and NDST2,
but not NDST3. In a Chinese hamster ovary cell mutant exhibiting
reduced N-sulfotransferase activity and reduced sulfation
of heparan sulfate (Bame, K. J., and Esko, J. D. (1989)
J. Biol. Chem. 264, 8059-8065), expression of NDST1
was greatly reduced, but NDST2 was expressed normally, suggesting that
both enzymes are involved in heparan sulfate assembly. The discovery of
multiple NDST isozymes suggests that the assembly of heparan sulfate is
much complicated than previously appreciated.
Molecular Cloning and Expression of a Third Member of the Heparan
Sulfate/Heparin GlcNAc
N-Deacetylase/ N-Sulfotransferase
Family
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
![]()
CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati What's this?
This article has been cited by other articles:
![]() |
J. R. Bishop, B. E. Crawford, and J. D. Esko Cell Surface Heparan Sulfate Promotes Replication of Toxoplasma gondii Infect. Immun., September 1, 2005; 73(9): 5395 - 5401. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. S. Saribas, A. Mobasseri, P. Pristatsky, X. Chen, R. Barthelson, D. Hakes, and J. Wang Production of N-sulfated polysaccharides using yeast-expressed N-deacetylase/N-sulfotransferase-1 (NDST-1) Glycobiology, December 1, 2004; 14(12): 1217 - 1228. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Lawrence, B. Kuberan, M. Lech, D. L. Beeler, and R. D. Rosenberg Mapping critical biological motifs and biosynthetic pathways of heparan sulfate Glycobiology, May 1, 2004; 14(5): 467 - 479. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Ashikari-Hada, H. Habuchi, Y. Kariya, N. Itoh, A. H. Reddi, and K. Kimata Characterization of Growth Factor-binding Structures in Heparin/Heparan Sulfate Using an Octasaccharide Library J. Biol. Chem., March 26, 2004; 279(13): 12346 - 12354. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Mochizuki, K. Yoshida, M. Gotoh, S. Sugioka, N. Kikuchi, Y.-D. Kwon, A. Tawada, K. Maeyama, N. Inaba, T. Hiruma, et al. Characterization of a Heparan Sulfate 3-O-Sulfotransferase-5, an Enzyme Synthesizing a Tetrasulfated Disaccharide J. Biol. Chem., July 11, 2003; 278(29): 26780 - 26787. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Jemth, E. Smeds, A.-T. Do, H. Habuchi, K. Kimata, U. Lindahl, and M. Kusche-Gullberg Oligosaccharide Library-based Assessment of Heparan Sulfate 6-O-Sulfotransferase Substrate Specificity J. Biol. Chem., June 27, 2003; 278(27): 24371 - 24376. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. J. Jenniskens, M. Ringvall, W. J. H. Koopman, J. Ledin, L. Kjellen, P. H. G. M. Willems, E. Forsberg, J. H. Veerkamp, and T. H. van Kuppevelt Disturbed Ca2+ kinetics in N-deacetylase/N-sulfotransferase-1 defective myotubes J. Cell Sci., June 1, 2003; 116(11): 2187 - 2193. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. van den Born, D. S. Pikas, B. J.M. Pisa, I. Eriksson, L. Kjellen, and J. H.M. Berden Antibody-based assay for N-deacetylase activity of heparan sulfate/heparin N-deacetylase/N-sulfotransferase (NDST): novel characteristics of NDST-1 and -2 Glycobiology, January 1, 2003; 13(1): 1 - 10. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. A. Strott Sulfonation and Molecular Action Endocr. Rev., October 1, 2002; 23(5): 703 - 732. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Grobe and J. D. Esko Regulated Translation of Heparan Sulfate N-Acetylglucosamine N-Deacetylase/N-Sulfotransferase Isozymes by Structured 5'-Untranslated Regions and Internal Ribosome Entry Sites J. Biol. Chem., August 16, 2002; 277(34): 30699 - 30706. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. C. Pedersen, T. A. Darden, and M. Negishi Crystal Structure of beta 1,3-Glucuronyltransferase I in Complex with Active Donor Substrate UDP-GlcUA J. Biol. Chem., June 7, 2002; 277(24): 21869 - 21873. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Yard, Y. Feng, H. Keller, C. Mall, and F. van der Woude Influence of high glucose concentrations on the expression of glycosaminoglycans and N-deacetylase/N-sulphotransferase mRNA in cultured skin fibroblasts from diabetic patients with or without nephropathy Nephrol. Dial. Transplant., March 1, 2002; 17(3): 386 - 391. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Li, N. W. Shworak, and M. Simons Increased responsiveness of hypoxic endothelial cells to FGF2 is mediated by HIF-1{alpha}-dependent regulation of enzymes involved in synthesis of heparan sulfate FGF2-binding sites J. Cell Sci., January 5, 2002; 115(9): 1951 - 1959. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Fukuda, N. Hiraoka, T. O. Akama, and M. N. Fukuda Carbohydrate-modifying Sulfotransferases: Structure, Function, and Pathophysiology J. Biol. Chem., December 14, 2001; 276(51): 47747 - 47750. [Full Text] [PDF] |
||||
![]() |
X. Bai, J. R. Brown, A. Varki, and J. D. Esko Enhanced 3-O-sulfation of galactose in Asn-linked glycans and Maackia amurenesis lectin binding in a new Chinese hamster ovary cell line Glycobiology, August 1, 2001; 11(8): 621 - 632. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. M. Pope, C. S. Raska, S. C. Thorp, and J. Liu Analysis of heparan sulfate oligosaccharides by nano-electrospray ionization mass spectrometry Glycobiology, June 1, 2001; 11(6): 505 - 513. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. J. Bame Heparanases: endoglycosidases that degrade heparan sulfate proteoglycans Glycobiology, June 1, 2001; 11(6): 91R - 98R. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Habuchi, M. Tanaka, O. Habuchi, K. Yoshida, H. Suzuki, K. Ban, and K. Kimata The Occurrence of Three Isoforms of Heparan Sulfate 6-O-Sulfotransferase Having Different Specificities for Hexuronic Acid Adjacent to the Targeted N-Sulfoglucosamine J. Biol. Chem., January 28, 2000; 275(4): 2859 - 2868. [Abstract] [Full Text] [PDF] |
||||
![]() |
K Prydz and K. Dalen Synthesis and sorting of proteoglycans J. Cell Sci., January 1, 2000; 113(2): 193 - 205. [Abstract] [PDF] |
||||
![]() |
F. Safaiyan, S. O. Kolset, K. Prydz, E. Gottfridsson, U. Lindahl, and M. Salmivirta Selective Effects of Sodium Chlorate Treatment on the Sulfation of Heparan Sulfate J. Biol. Chem., December 17, 1999; 274(51): 36267 - 36273. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. E. Stringer, M. Mayer-Proschel, A. Kalyani, M. Rao, and J. T. Gallagher Heparin Is a Unique Marker of Progenitors in the Glial Cell Lineage J. Biol. Chem., September 3, 1999; 274(36): 25455 - 25460. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. Bai, G. Wei, A. Sinha, and J. D. Esko Chinese Hamster Ovary Cell Mutants Defective in Glycosaminoglycan Assembly and Glucuronosyltransferase I J. Biol. Chem., May 7, 1999; 274(19): 13017 - 13024. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Ringvall, J. Ledin, K. Holmborn, T. van Kuppevelt, F. Ellin, I. Eriksson, A.-M. Olofsson, L. Kjellen, and E. Forsberg Defective Heparan Sulfate Biosynthesis and Neonatal Lethality in Mice Lacking N-Deacetylase/N-Sulfotransferase-1 J. Biol. Chem., August 18, 2000; 275(34): 25926 - 25930. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Ouzzine, S. Gulberti, P. Netter, J. Magdalou, and S. Fournel-Gigleux Structure/Function of the Human Galbeta 1,3-glucuronosyltransferase. DIMERIZATION AND FUNCTIONAL ACTIVITY ARE MEDIATED BY TWO CRUCIAL CYSTEINE RESIDUES J. Biol. Chem., September 1, 2000; 275(36): 28254 - 28260. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Hiraoka, H. Nakagawa, E. Ong, T. O. Akama, M. N. Fukuda, and M. Fukuda Molecular Cloning and Expression of Two Distinct Human Chondroitin 4-O-Sulfotransferases That Belong to the HNK-1 Sulfotransferase Gene Family J. Biol. Chem., June 23, 2000; 275(26): 20188 - 20196. [Abstract] [Full Text] [PDF] |
||||
![]() |
J.-i. Aikawa, K. Grobe, M. Tsujimoto, and J. D Esko Multiple Isozymes of Heparan Sulfate/Heparin GlcNAc N-Deacetylase/GlcN N-Sulfotransferase. STRUCTURE AND ACTIVITY OF THE FOURTH MEMBER, NDST4 J. Biol. Chem., February 16, 2001; 276(8): 5876 - 5882. [Abstract] [Full Text] [PDF] |
||||
![]() |
J.-P. Li, F. Gong, K. El Darwish, M. Jalkanen, and U. Lindahl Characterization of the D-Glucuronyl C5-epimerase Involved in the Biosynthesis of Heparin and Heparan Sulfate J. Biol. Chem., June 1, 2001; 276(23): 20069 - 20077. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Zhang, R. Lawrence, J. J. Schwartz, X. Bai, G. Wei, J. D. Esko, and R. D. Rosenberg The Effect of Precursor Structures on the Action of Glucosaminyl 3-O-Sulfotransferase-1 and the Biosynthesis of Anticoagulant Heparan Sulfate J. Biol. Chem., July 27, 2001; 276(31): 28806 - 28813. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. L. R. Merry, S. L. Bullock, D. C. Swan, A. C. Backen, M. Lyon, R. S. P. Beddington, V. A. Wilson, and J. T. Gallagher The Molecular Phenotype of Heparan Sulfate in the Hs2st-/- Mutant Mouse J. Biol. Chem., September 14, 2001; 276(38): 35429 - 35434. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |