Biosynthesis of Heparan Sulfate and Heparin. How Are the Multifunctional Glycosaminoglycans Built up?

Habuchi, Hiroko; Habuchi, Osami; Kimata, Koji

doi:10.4052/tigg.10.65

Cited by 19 publications

(11 citation statements)

References 38 publications

(37 reference statements)

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“…5). These results confirm the previous conclusions that 5Ј-phosphosulfate and 3Ј-phosphate binding sites are critical for the binding to PAPS (25)(26)(27)(28).…”

Section: Discussionsupporting

confidence: 92%

“…When we compared the amino acid sequence of HNK-1ST to those of Golgi-associated sulfotransferases cloned before (21-24), we noticed that amino acid sequence motifs, including the sequence RDP, are shared by those enzymes (18). Although we did not initially detect its homology with cytosolic sulfotransferases, subsequent studies revealed that there are two regions in the catalytic domain that are shared by all sulfotransferases cloned so far (25,26). This homology was also proposed because the crystal structure of a mouse estrogen sulfotransferase became available (27), and the amino acid residues involved in the interaction with the 5Ј-phosphosulfate or 3Ј-phosphate group of PAPS were identified (Fig.…”

mentioning

confidence: 90%

“…1). The studies thus revealed that a lysine or arginine residue is shared by all sulfotransferases cloned to date in the 5Ј-phosphosulfate binding (5Ј-PSB) 1 site and an arginine residue is shared by almost all sulfotransferases at the 3Ј-phosphate binding (3Ј-PB) motif (25)(26)(27). Moreover, the entirely conserved serine residue at the 3Ј-PB loop apparently provides a hydrogen bond with a hydroxyl group of 3Ј-phosphate (27).…”

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confidence: 99%

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Structure and Function of HNK-1 Sulfotransferase

Ong¹,

Yeh²,

Ding³

et al. 1999

Journal of Biological Chemistry

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HNK-1 glycan, sulfo33GlcA␤133Gal␤134GlcNAc3 R, is uniquely enriched in neural cells and natural killer cells and is thought to play important roles in cell-cell interaction. HNK-1 glycan synthesis is dependent on HNK-1 sulfotransferase (HNK-1ST), and cDNAs encoding human and rat HNK-1ST have been recently cloned. HNK-1ST belongs to the sulfotransferase gene family, which shares two homologous sequences in their catalytic domains. In the present study, we have individually mutated amino acid residues in these conserved sequences and determined how such mutations affect the binding to the donor substrate, adenosine 3-phosphate 5-phosphosulfate, and an acceptor. were conservatively mutated to Arg and Glu, respectively, however, the mutated enzymes still maintained residual activity, and both mutant enzymes still bound to adenosine 3,5-diphosphate-agarose. K128R and D190E mutant enzymes, on the other hand, exhibited reduced affinity to the acceptor as demonstrated by kinetic studies. These findings, together with those on the crystal structure of estrogen sulfotransferase and heparan sulfate N-deacetylase/sulfotransferase, suggest that Lys 128 may be close to the 3-hydroxyl group of ␤-glucuronic acid in a HNK-1 acceptor. In contrast, the effect by mutation at Asp 190 may be due to conformational change because this amino acid and Pro 191 reside in a transition of the secondary structure of the enzyme. These results indicate that conserved amino acid residues in HNK-1ST play roles in maintaining a functional conformation and are directly involved in binding to donor and acceptor substrates.HNK-1 glycan is a unique carbohydrate expressed in a celltype specific manner (1, 2). In particular, HNK-1 glycan has been found in a number of neural cell adhesion molecules including the neural cell adhesion molecule, myelin-associated glycoprotein, L1, contactin, and P0 (3-7). Carbohydrate structural analysis of P0 showed that HNK-1 glycan is present in biantennary bisected N-glycan as sulfo3 GlcA␤133Gal-␤134GlcNAc␤132Man␣136[R3 Man␣133(GlcNAc␤134)]-Man␤134GlcNAc␤134GlcNAc3 Asn (8). The capping structure of this HNK-1 epitope is the same as those found in glycolipids such as sulfo33GlcA␤133Gal␤134GlcNAc␤133-Gal␤134Glc␤3ceramide (9, 10). The expression of HNK-1 glycan is spatially and temporally regulated and is found on migrating neural crest cells, cerebellum, and myelinating Schwann cells in motor neurons but not on those in the sensory neurons (11-13). Neural outgrowth of mouse motor neurons was facilitated much better by HNK-1 glycolipid substratum than sulfatide or GD1b ganglioside substratum (14). Complementary to this finding, the inhibition of neurite outgrowth by HNK-1 glycan was not observed once the sulfate group was removed (15). It has also been shown that the homophilic interaction of P0 depends on carbohydrate-protein interaction and anti-HNK-1 antibody inhibits this interaction (16,17).To elucidate the roles of HNK-1 glycan in molecular details, we and others have cloned a sulfotransferase HNK-1ST that forms HNK-...

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“…5). These results confirm the previous conclusions that 5Ј-phosphosulfate and 3Ј-phosphate binding sites are critical for the binding to PAPS (25)(26)(27)(28).…”

Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 90%

mentioning

confidence: 99%

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Structure and Function of HNK-1 Sulfotransferase

Ong¹,

Yeh²,

Ding³

et al. 1999

Journal of Biological Chemistry

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“…In the case of heparin, a series of five enzymatic activities is coordinated: N-deacetylase followed by N-sulfotransferase and then O-sulfotransferase and GlcA C5-epimerase [370,385]. The first two activities are harbored in one protein for which mouse tissues express two different genes [386].…”

Section: Review Articlementioning

confidence: 99%

Eukaryotic glycosylation: whim of nature or multipurpose tool?

Reuter¹,

Gabius²

1999

Cellular and Molecular Life Sciences (CMLS)

214

141

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Protein and lipid glycosylation is a ubiquitous phenomenon. The task of cataloguing the great structural variety of the glycan part has demanded considerable efforts over decades. This patient endeavor was imperative to discern the inherent rules of glycosylation which cannot affirm assumptions on a purely coincidental nature of this type of protein and lipid modification. These results together with theoretical considerations uncover a salient property of oligosaccharides. In comparison with amino acids and nucleotides, monosaccharides excel in their potential to serve as units of hardware for storing biological information. Thus, the view that glycan chains exclusively affect physiochemical properties of the conjugates is indubitably flawed. This original concept has been decisively jolted by the discovery of endogenous receptors (lectins) for distinct glycan epitopes which are as characteristic as a fingerprint or a signature for a certain protein (class) or cell type. Recent evidence documents that these binding proteins are even endowed with the capacity to select distinct low-energy conformers of the often rather flexible oligosaccharides, granting entry to a new level of regulation of ligand affinity by shifting conformer equilibria. The assessment of the details of this recognition by X-ray crystallography, nuclear magnetic resonance spectroscopy, microcalorimetry and custom-made derivatives is supposed to justify a guarded optimism in satisfying the need for innovative drug design in antiadhesion therapy, for example against viral or bacterial infections and unwanted inflammation. This review presents a survey of the structural aspects of glycosylation and of evidence to poignantly endorse the notion that carrier-attached glycan chains can partake in biological information transfer at the level of cell compartments, cells and organs.

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“…Furthermore, biochemical studies have shown how interactions of cell-surface HSPGs can be speci®c at various levels. Tissue-speci®c isoforms of the polymerizing and chainmodifying enzymes can produce HS chains with distinct sequences and macroscopic organizations 3,4 . Various ligands and their receptors can show selectivity in their binding af®nities to distinct HS chain structures 5,6 .…”

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confidence: 99%

Specificities of heparan sulphate proteoglycans in developmental processes

Perrimon

Bernfield

2000

Nature

679

508

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Heparan sulphate proteoglycans are abundant cell-surface molecules that consist of a protein core to which heparan sulphate glycosaminoglycan chains are attached. The functions of these molecules have remained mostly underappreciated by developmental biologists; however, the actions of important signalling molecules, for example Wnt and Hedgehog, depend on them. To understand both the mechanisms by which ligands involved in development interact with their receptors and how morphogens pattern tissues, biologists need to consider the functions of heparan sulphate proteoglycans in signalling and developmental patterning.

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Biosynthesis of Heparan Sulfate and Heparin. How Are the Multifunctional Glycosaminoglycans Built up?

Cited by 19 publications

References 38 publications

Structure and Function of HNK-1 Sulfotransferase

Structure and Function of HNK-1 Sulfotransferase

Eukaryotic glycosylation: whim of nature or multipurpose tool?

Specificities of heparan sulphate proteoglycans in developmental processes

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