Molecular Cloning and Characterization of a Human Uronyl 2-Sulfotransferase That Sulfates Iduronyl and Glucuronyl Residues in Dermatan/Chondroitin Sulfate

Kobayashi, Masashi; Sugumaran, Geetha; Liu, Jian; Shworak, Nicholas W.; Silbert, Jeremiah E.; Rosenberg, Robert D.

doi:10.1074/jbc.274.15.10474

Cited by 134 publications

(95 citation statements)

References 46 publications

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“…This result correlates well with the mRNA data, since this enzyme has only one isoform in most of the genome-sequenced organisms, in contrast to multiple isoforms for almost all other HS and CS sulfotransferases [39]. CS-2OST transfers the sulfo group to the 2-OH position of the hexuronic acid that is adjacent to an Nacetylated galactosamine residue (GalNAc) carrying either a 6-O or 4-O sulfo group [41,42] and CS chains with 2-O-sulfo group exhibits a variety of biological functions [43,44,45]. In pre-eclampsia, the absence of 2-O-sulfo groups may reflect the fine tuning of CS chain that normally occurs in gravid placenta.…”

Section: Discussionsupporting

confidence: 74%

Is human placenta proteoglycan remodeling involved in pre-eclampsia?

et al. 2007

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Impaired placento-fetal communication is a coherent symptom of exaggerated pre-eclampsia. The impact of the cellular expression of different glycosaminoglycans (GAGs) in this event on the placenta in pre-eclampsia is still obscure. This is the first study aimed at discovering the relationship between structural alterations of different sulfated GAGs at the molecular level and the development of pre-eclampsia in inflicted placenta. Sulfated GAGs were isolated and purified from control and pre-eclampsia placentas. The amount and the molecular weight of GAG in each tissue sample were measured. The polydispersity of the recovered GAG samples were determined by polyacrylamide gel electrophoresis. The disaccharide composition of chondroitin sulfate, dermatan sulfate and heparan sulfate were deduced by chondroitinase and heparinase depolymerization followed by liquid chromatography-mass spectrometry. The in vivo sulfo-modulation of GAGs in pre-eclampsia and control placenta were examined using RT-PCR to determine the transcription levels of different sulfotransferases involved in GAG biosynthesis. Marked differences in GAG sulfation patterns and mRNA level of encoding selected GAG O-sulfotransferases were observed in pre-eclampsia. These data suggest a linkage between pre-eclampsia and the observed alterations in placental GAGs and could provide new insights about the modulating role of GAGs in the development and the severity of placental pre-eclampsia.

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Section: Discussionsupporting

confidence: 74%

Is human placenta proteoglycan remodeling involved in pre-eclampsia?

et al. 2007

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“…This conclusion is supported by the finding that recombinant 2-OST will sulphate GlcA residues in an exogenous (-GlcA-GlcNSO $ -) n acceptor polysaccharide of the appropriate structure (J. Rong, H. Habuchi, K. Kimata, U. Lindahl and M. Kusche-Gullberg, unpublished work). Similar findings were recently reported for a 2-OST capable of sulphating both GlcA and IdoA units in chondroitin\dermatan sulphate [20]. Notably, a mutant CHO cell line deficient in 2-OST activity was found to lack both IdoA(2-OSO $ ) and GlcA(2-OSO $ ) units [21].…”

Section: Discussionsupporting

confidence: 70%

Expression of heparan sulphate l-iduronyl 2-O-sulphotransferase in human kidney 293 cells results in increased d-glucuronyl 2-O-sulphation

Habuchi

Kimata

Lindahl

et al. 2000

Biochemical Journal

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Functionally important interactions between heparan sulphate and a variety of proteins depend on the precise location of O-sulphate groups. Such residues occur at C-2 of L-iduronic (IdoA) and D-glucuronic acid (GlcA) units, and at C-3 and C-6 of D-glucosamine (GlcN) units. Stable transfection of human embryonic kidney 293 cells with a cDNA encoding mouse mastocytoma IdoA 2-O-sulphotransferase resulted in an approx. 6-fold increase in O-sulphotransferase activity, compared with control cells, as determined using O-desulphated heparin as an acceptor. Structural analysis of endogenous heparan sulphate in the transfected cells, following metabolic labelling with either [3H]GlcN or [35S]sulphate, showed appreciable formation of -GlcA(2-OSO3)-GlcNSO3- disaccharide units (6% of total disaccharide units; 17% of total O-sulphated disaccharide units) that were essentially absent from heparan sulphate from control cells. The increase in GlcA 2-O-sulphation was accompanied by a decrease in the amount of IdoA formed, whereas overall 2-O-sulphation or 6-O-sulphation remained largely unaffected. These findings indicate that 2-O-sulphation of IdoA and GlcA residues is catalysed by the same enzyme in heparan sulphate biosynthesis.

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“…Completely desulfated, N -sulfated-heparin and low sulfated HS from mouse tumors are good acceptors whereas there is no activity towards CS or DS. HS2ST is distinct from the uronyl 2-O-sulfotransferase for the synthesis of CS/DS (82). A CHO cell mutant, pgsF-17, defective in HS2ST, produces HS chains lacking not only IdoA(2-O-sulfate)-N -sulfoglucosamine and IdoA(2-O-sulfate)-N -sulfoglucosamine(6-O-sulfate) but also GlcA(2-O-sulfate)-N -sulfoglucosamine (83).…”

Section: Biosynthetic Events Modifiying the Glycosylaminoglycan Backbonementioning

confidence: 99%

Heparin and Heparan Sulfate Biosynthesis

2002

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SummaryHeparan sulfate is one of the most informationally rich biopolymers in Nature. Its simple sugar backbone is variously modified to different degrees depending on the cellular conditions. Thus, it matures to have an enormously complicated structure, which most likely exhibits a considerable number of unique overlapping sequences with peculiar sulfation profiles. Such sequences are recognized by specific complementary proteins, which form a huge group of "heparin-binding proteins," and the sugar sequences in turn support unique functions of the respective proteins through specific interactions. The heparan sulfate sequences are not directly encoded by genes, but are created by elaborate biosynthetic mechanisms, which ensure the generation of these indispensable sequences. In heparan sulfate biosynthesis, the tetrasaccharide sequence (GlcAGal-Gal-Xyl-), designated the protein linkage region, is first assembled on a specific Ser residue at the glycosaminoglycan attachment site of a core protein. A heparan sulfate chain is then polymerized on this fragment by alternate additions of GlcNAc and GlcA through the actions of glycosyltransferases with overlapping specificities encoded by the tumor suppressor EXT family genes. Then follow various modifications by N-deacetylation and N-sulfation of glucosamine, C5-epimerization of GlcA and multiple O-sulfations of the component sugars. Recent studies have achieved purification of several, and molecular cloning of most, of the enzymes responsible for these reactions. Some of these enzymes are bifunctional. The availability of cDNA probes has facilitated elucidation of the crystal structures for two of the biosynthetic enzymes, demonstration of their intracellular location, and their occurrence in complexes to achieve rapid and efficient synthesis of complex sugar sequences. Genomic structure and transcript analysis have shown the existence of multiple isoforms for most of the sulfotransferases. Many aspects of the heparan sulfate biosynthetic scheme are shared by the structural analog heparin, which is synthesized in mast cells and some other mammalian cells and is several-fold higher degree of polymerization and more extensive modification than heparan sulfate.

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Molecular Cloning and Characterization of a Human Uronyl 2-Sulfotransferase That Sulfates Iduronyl and Glucuronyl Residues in Dermatan/Chondroitin Sulfate

Abstract: A partial-length human cDNA with a predicted amino acid sequence homologous to a previously described heparan sulfate iduronyl 2-sulfotransferase (Kobayashi, M., Habuchi, H., Yoneda, M., Habuchi, O., and Kimata, K.

Cited by 134 publications

References 46 publications

Is human placenta proteoglycan remodeling involved in pre-eclampsia?

Is human placenta proteoglycan remodeling involved in pre-eclampsia?

Expression of heparan sulphate l-iduronyl 2-O-sulphotransferase in human kidney 293 cells results in increased d-glucuronyl 2-O-sulphation

Heparin and Heparan Sulfate Biosynthesis

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