Conformer populations of l-iduronic acid residues in glycosaminoglycan sequences

Ferro, Dino R.; Provasoli, Augusto; Ragazzi, Massimo; Casu, Benito; Torri, Giangiacomo; Bossennec, V; Perly, Bruno; Sînaÿ, Pierre; Petitou, Maurice; Choay, J

doi:10.1016/0008-6215(90)84164-p

Cited by 229 publications

(205 citation statements)

References 21 publications

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“…AH-Sepharose, Sephadex G-25, Red-Sepharose, and ConA-Sepharose gels, Mono-Q 5/5, Superose 12 HR 10/30, Mono-Q PC 1.6/5 (operated with Smart System), Superdex Peptide 10/300 GL, and PD-10 columns were obtained from Amersham Biosciences, as was D- [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]glucose (57 mCi/ mmol). D- [5-3 H]Glucose (20 Ci/mmol) was from PerkinElmer Life Sciences, and inorganic carrier-free […”

Section: Methodsmentioning

confidence: 99%

“…Enzyme samples, containing 3 mg of BSA as carrier unless otherwise stated, were desalted at 4°C on Sephadex G-25 columns (0.7 ϫ 3 cm), equilibrated with desalting buffer (20 mM MES (pH 5.5 at 37°C), 10% glycerol, 0.5 mM EDTA, 0.1% Triton X-100, 1 mM DTT, protease inhibitors). Incubations were performed in a 100-l final volume of 0.8ϫ desalting buffer, 0.5 mg of BSA, 2 mM MnCl 2 , 0.5% Nonidet P-40, and 30,000 dpm H]dK4 or [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]dK4 (ϳ200 M HexA for both substrates). Incubations were done at 37°C for 2-14 h and stopped by boiling for 5 min, and samples were centrifuged.…”

Section: Methodsmentioning

confidence: 99%

“…It is important to define the CS/DS structures involved in selective protein binding and to understand how they are generated. The IdoUA-containing domains of DS chains are of particular significance in this regard, because IdoUA residues endow conformational flexibility to the polymer, which is believed to facilitate protein interactions (10).…”

mentioning

confidence: 99%

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Biosynthesis of Dermatan Sulfate

Maccarana

Olander

Malmström

et al. 2006

Journal of Biological Chemistry

138

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We identified the gene encoding chondroitin-glucuronate C5-epimerase (EC 5.1.3.19) that converts D-glucuronic acid to L-iduronic acid residues in dermatan sulfate biosynthesis. The enzyme was solubilized from bovine spleen, and an ϳ43,000-fold purified preparation containing a major 89-kDa candidate component was subjected to mass spectrometry analysis of tryptic peptides. SART2 (squamous cell carcinoma antigen recognized by T cell 2), a protein with unknown function highly expressed in cancer cells and tissues, was identified by 18 peptides covering 26% of the sequence. Transient expression of cDNA resulted in a 22-fold increase in epimerase activity in 293HEK cell lysate. Moreover, overexpressing cells produced dermatan sulfate chains with 20% of iduronic acid-containing disaccharide units, as compared with 5% for mock-transfected cells. The iduronic acid residues were preferentially clustered in blocks, as in naturally occurring dermatan sulfate. Given the discovered identity, we propose to rename SART2 (Nakao, M., Shichijo, S., Imaizumi, T., Inoue, Y., Matsunaga, K., Yamada, A., Kikuchi, M., Tsuda, N., Ohta, K., Takamori, S., Yamana, H., Fujita, H., and Itoh, K. (2000) J. Immunol. 164, 2565-2574) with a functional designation, chondroitin-glucuronate C5-epimerase (or DS epimerase). DS epimerase activity is ubiquitously present in normal tissues, although with marked quantitative differences. It is highly homologous to part of the NCAG1 protein, encoded by the C18orf4 gene, genetically linked to bipolar disorder. NCAG1 also contains a putative chondroitin sulfate sulfotransferase domain and thus may be involved in dermatan sulfate biosynthesis. The functional relation between dermatan sulfate and cancer is unknown but may involve known iduronic acid-dependent interactions with growth factors, selectins, cytokines, or coagulation inhibitors. Proteoglycans consist of glycosaminoglycan (GAG)5 chains covalently linked to core proteins. The GAGs play important roles in mediating biological functions of proteoglycans, mainly due to their ability to interact with a variety of proteins (1-5). Chondroitin sulfate (CS)/dermatan sulfate (DS) proteoglycans carry GAGs composed of alternating units of GalNAc and GlcA, or IdoUA in the case of DS. The chondroitin/CS/DS family has been ascribed a variety of physiological/developmental effects that range from control of basic cellular processes such as cell division in Caenorhabditis elegans, scaffold functions in various types of connective tissue, to highly cell type-specific effects, as exemplified by the neurite outgrowthpromoting activity mediated by rare structures in cerebral CS/DS (6 -9). Protein ligands targeted by CS/DS include growth factors, modulators of blood coagulation, selectins, and chemokines. It is important to define the CS/DS structures involved in selective protein binding and to understand how they are generated. The IdoUA-containing domains of DS chains are of particular significance in this regard, because IdoUA residues endow conformational flexibili...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Biosynthesis of Dermatan Sulfate

Maccarana

Olander

Malmström

et al. 2006

Journal of Biological Chemistry

138

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“…The flexibility of iduronic acid, which can be found as (Ferro et al 1990), is thought to facilitate protein binding. For instance, hepatocyte growth factor/scatter factor (HGF/SC) requires IdoA residue flanked by sulfated hexosamine (Deakin et al 2009).…”

Section: Functions Of Iduronic Acid In Cs/ds Proteoglycansmentioning

confidence: 99%

Iduronic Acid in Chondroitin/Dermatan Sulfate

Malmström

Bartolini

Thelin

et al. 2012

J Histochem Cytochem.

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The ability of chondroitin/dermatan sulfate (CS/DS) to convey biological information is enriched by the presence of iduronic acid. DS-epimerases 1 and 2 (DS-epi1 and 2), in conjunction with DS-4-O-sulfotransferase 1, are the enzymes responsible for iduronic acid biosynthesis and will be the major focus of this review. CS/DS proteoglycans (CS/DS-PGs) are ubiquitously found in connective tissues, basement membranes, and cell surfaces or are stored intracellularly. Such wide distribution reflects the variety of biological roles in which they are involved, from extracellular matrix organization to regulation of processes such as proliferation, migration, adhesion, and differentiation. They play roles in inflammation, angiogenesis, coagulation, immunity, and wound healing. Such versatility is achieved thanks to their variable composition, both in terms of protein core and the fine structure of the CS/DS chains. Excellent reviews have been published on the collective and individual functions of each CS/DS-PG. This short review presents the biosynthesis and functions of iduronic acid-containing structures, also as revealed by the analysis of the DS-epi1- and 2-deficient mouse models.

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“…In contrast to heparin, 100% yields were found at all pHs chloramide yield as found in the model compound. The 3-dimensional structure of heparin [31,32] shows that the 6-O-sulphate group is closer to the N-sulphate group than is the 2-O-sulphate group in the ioduronic acid moiety and is therefore likely to produce a greater negative electrostatic effect on the rate of reaction of OCl -with the N-sulphate group. This effect is clearly sufficient to allow an oxidation step to be preferred in 40% of the OCl -reaction with heparin at pH8.5, in contrast to no oxidation in the D-glucosamine-2-N-sulphate model compound.…”

Section: Reaction Of Hypochlorite With Model Monosaccharidesmentioning

confidence: 99%

Chlorination and oxidation of heparin and hyaluronan by hypochlorous acid and hypochlorite anions: effect of sulfate groups on reaction pathways and kinetics

Akeel

Sibanda

Martin

et al. 2013

Free Radical Biology and Medicine

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Hypochlorous acid (HOCl), produced in inflammatory conditions by the enzyme myeloperoxidase, and its anion, perchlorite ( OCl -) exist in vivo at almost equal concentrations. Their reactions with hyluronan and heparin (as a model for sulphated glycosaminoglycans in the extracellular matrix), have been studied as a function of pH. The major product in these reactions is the chloramide derivative of the glycosaminoglycans. Spectral, chloramide yield and kinetic measurements show sharply contrasting behaviour of heparin and hyaluronan and the data allow the calculation of second-order rate constants for the reactions of both HOCl and OCl -for all reaction pathways leading to the formation of chloramides and also oxidation products . By comparison with hyaluronan, it can be demonstrated that both N-sulphate and O-sulphate groups in heparin influence the proportions of these pathways in this glycosaminoglycan. Evidence is also given for further oxidation pathways involving a reaction of HOCl with the chloramide product of hyaluronan but not with heparin. The significance of these results for mechanisms of inflammation, particularly for fragmentation of extracellular matrix glycosaminoglycans is discussed.

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Conformer populations of l-iduronic acid residues in glycosaminoglycan sequences

Cited by 229 publications

References 21 publications

Biosynthesis of Dermatan Sulfate

Biosynthesis of Dermatan Sulfate

Iduronic Acid in Chondroitin/Dermatan Sulfate

Chlorination and oxidation of heparin and hyaluronan by hypochlorous acid and hypochlorite anions: effect of sulfate groups on reaction pathways and kinetics

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