Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.6.4 (chondroitinase)
 2,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Shark cartilage proteoglycans bear predominantly chondroitin 6-sulfate. After exhaustive protease digestion, reductive beta-elimination, and subsequent chondroitinase ABC digestion, 13 hexasaccharide alditols, which are nonsulfated, sulfated, and/or phosphorylated, were obtained from the carbohydrate-protein linkage region. Six compounds, containing 0 or 1 sulfate and/or phosphate residue, represent approximately 40% of the isolated linkage hexasaccharide alditols. They were analyzed by chondroitinase ACII or alkaline phosphatase digestion in conjunction with high performance liquid chromatography, and by 500 MHz one- and two-dimensional 1H NMR spectroscopy. All six compounds have the conventional structure in common. Delta 4,5-GlcA beta 1-3GalNAc beta 1-4GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl-ol One compound has no sulfate nor phosphate. Two of the monosulfated compounds have a O-sulfate on C-6 or on C-4 of the GalNAc residue. The third monosulfated compound has a novel O-sulfate on C-6 of the Gal residue attached to xylitol. The two phosphorylated compounds have O-phosphate on C-2 of Xyl-ol, and one of them has in addition sulfate on C-6 of GalNAc.
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PMID:Structural studies on sulfated oligosaccharides derived from the carbohydrate-protein linkage region of chondroitin 6-sulfate proteoglycans of shark cartilage. I. Six compounds containing 0 or 1 sulfate and/or phosphate residues. 155 14

The structure of the linkage region of chondroitin sulfate chains attached to the hybrid proteoglycans of the Engelbreth-Holm-Swarm mouse tumor was investigated. The peptidoglycan fraction which contains oversulfated chondroitin sulfate rich in the GlcA beta 1-3GalNAc-4,6-diO-sulfate unit and undersulfated heparan sulfate rich in GlcA beta 1-4GlcNAc and GlcA beta 1-4GlcN-2N-sulfate units was isolated after exhaustive protease digestion of the acetone powder of the tumor tissue, (GlcA, glucuronic acid; GalNAc, 2-deoxy-2-N-acetylamino-D-galactose). Glycosaminoglycans were released by beta-elimination using NaB3H4 and digested with chondroitinase ABC. The linkage region fraction was separated from heparan sulfate by gel filtration and fractionated by HPLC on an amine-bound silica column. Six radiolabeled compounds (L1-L6) were obtained and structurally analyzed by cochromatography with authentic hexasaccharide alditols recently isolated by us from the linkage region, and by digestion using chondroitinase ACII, alkaline phosphatase and beta-galactosidase in conjugation with HPLC. These compounds shared the conventional hexasaccharide backbone structure: delta GlcA beta 1-3GalNAc beta 1-4GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl-ol, (delta GlcA, delta 4.5-GlcA or D-gluco-4-enepyranosyluronic acid). L1 was not sulfated or phosphorylated. L2 and L4 were monosulfated at C-6 and C-4 of the GalNAc residue, respectively. Upon alkaline phosphatase digestion, L3, L5 and L6 were converted to L1, L2 and L4, respectively. Analysis of the periodate oxidation products indicated that the phosphate group in L3, L5 and L6 is located at C-2 of Xyl-ol. These results suggest that Xyl-2-O-phosphate is associated with both 4-O-sulfated and 6-O-sulfated GalNAc units and does not directly determine the sulfation pattern of chondroitin sulfate.
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PMID:The phosphorylated and/or sulfated structure of the carbohydrate-protein-linkage region isolated from chondroitin sulfate in the hybrid proteoglycans of Engelbreth-Holm-Swarm mouse tumor. 174 Jan 53

From the carbohydrate-protein linkage region of whale cartilage proteoglycans, which bear predominantly chondroitin 4-sulfate, one nonsulfated, two monosulfated and one disulfated hexasaccharide alditols were isolated after exhaustive digestions with Actinase E and chondroitinase ABC, and subsequent beta-elimination. Their structures were analyzed by chondroitinase ACII digestion in conjunction with HPLC and by 500-MHz 1H-NMR spectroscopy. The nonsulfated compound (A) had the following conventional structure: delta GlcA(beta 1-3)-GalNAc(beta 1-4)GlcA(beta 1-3)Gal(beta 1-4)Xylol, where GlcA, delta GlcA and GalNAc are glucuronic acid; 4,5-unsaturated glucuronic acid and 2-deoxy-2-N-acetylamino-D-galactose, respectively. The other compounds were sulfated derivatives of compound A. Two monosulfated compounds (B and C) had an ester sulfate on C4 or C6 of the GalNAc residue, respectively and the disulfated compound (D) had two ester sulfate groups, namely, one on C4 of the GalNAc and the other on C4 of the Gal residue substituted by GlcA. The molar ratio of A/B/C/D was 0.21:0.16:0.36:0.27. The compound containing Gal-4-O-sulfate was previously isolated by us in the form of a sulfated glycoserine [delta GlcA(beta 1-3)GalNAc(4-O- sulfate)(beta 1-4)GlcA(beta 1-3)Gal(4-O-sulfate)(beta 1-3)-Gal(beta 1- 4)Xyl beta 1-O-Ser] from the carbohydrate-protein linkage region of rat chondrosarcoma chondroitin-4-sulfate proteoglycans [Sugahara K., Yamashina, I., DeWaard, P., Van Halbeek, H. & Vliegenthart, J.F.G. (1988) J. Biol. Chem. 263, 10,168-10,174]. The discovery of this structure in the carbohydrate-protein linkage region of chondroitin 4-sulfate proteoglycans from nontumorous cartilage indicates that it is not a tumor-associated product but rather a physiological biosynthetic product since it represents a significant proportion. The biological significance of this structure is discussed in relation to glycosaminoglycan biosynthesis.
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PMID:Structural studies on sulfated oligosaccharides derived from the carbohydrate-protein linkage region of chondroitin sulfate proteoglycans of whale cartilage. 176 94

Keratan sulphate chains were isolated from bovine tracheal ring cartilage (15-18-month-old animals) after papain digestion of the tissue followed by ethanol fractionation, chondroitinase ABC digestion and alkaline borohydride reduction. The keratan sulphate chains were further purified by anion-exchange chromatography on a Pharmacia Mono-Q column in order to remove any contaminating chondroitin sulphate and O-linked oligosaccharides. The chains were then treated with keratanase and the digest was subjected to alkaline borohydride reduction, producing oligosaccharides with galactitol at their reducing ends. The reduced digest was chromatographed on a Nucleosil 5 SB anion-exchange column and individual oligosaccharides were isolated. One of these, oligosaccharide (I), was shown by 500 MHz 1H-n.m.r. spectroscopy to have the following structure: NeuAc alpha 2-3Gal beta 1-4GlcNAc(6SO4) beta 1-3Gal-ol (I) The structure of this oligosaccharide shows that keratan sulphate chains from bovine tracheal ring cartilage may be terminated with N-acetylneuraminic acid linked alpha (2-3) to an unsulphated galactose. Keratan sulphate chains were also isolated from bovine femoral head cartilage (15-18-month-old animals) using an identical protocol, but with keratanase which was subsequently shown to have sialidase activity. This yielded oligosaccharide (II), the unsialyated version of (I): Gal beta 1-4GlcNAc(6SO4) beta 1-3Gal-ol (II).
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PMID:A non-reducing terminal fragment from tracheal cartilage keratan sulphate chains contains alpha (2-3)-linked N-acetylneuraminic acid. 191 Mar 36

Two major proteoglycans, which appear to be structurally closely related, were isolated from bovine chromaffin granule matrix proteins by ion-exchange chromatography. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis they have apparent average molecular sizes of 35-40 kDa (range of 23-75 kDa) and generate a 14-kDa core glycoprotein after chondroitinase treatment. Previous studies demonstrated that these two major chromaffin granule proteoglycans are very similar in terms of their peptide mapping patterns and carbohydrate composition (having a high proportion of tri- and tetraantennary N-glycosidic oligosaccharides, and O-glycosidic oligosaccharides consisting predominantly of disialyl derivatives of galactosyl(beta 1-3)N-acetylgalactosamine), and that they differed in these respects from the chromogranins. By using antisera to five synthetic peptide fragments of chromogranin A to stain immunoblots of purified chromaffin granule proteoglycans before and after chondroitinase treatment, we have now shown that these major proteoglycans are not immunochemically related to chromogranin A. However, it has recently been reported that some chromogranin A-immunoreactive material disappears after chondroitinase treatment, and our studies demonstrate that approximately 1-2% of the chromogranin A occurs in the form of a 110-kDa proteoglycan, which is converted to a 95-kDa core glycoprotein after chondroitinase treatment. Similar chromogranin A proteoglycans could be detected in rat PC12 pheochromocytoma cells, where they have a molecular size of 115-145 kDa and yield a 105-kDa core protein after chondroitinase treatment. Studies using antibodies to synthetic peptide fragments of chromogranin B (secretogranin I) did not provide any evidence that this related protein occurs in a proteoglycan form.
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PMID:Chromaffin granule and PC12 cell chondroitin sulfate proteoglycans and their relation to chromogranin A. 239 98

Monoclonal antibodies produced against chick embryo limb bud proteoglycan (PG-M) were selected for their ability to recognize determinants on intact chondroitin sulfate chains. One of these monoclonal antibodies (IgM; designated MO-225) reacts with PG-M, chick embryo cartilage proteoglycans (PG-H, PG-Lb, and PG-Lt), and bovine nasal cartilage proteoglycan, but not with Swarm rat chondrosarcoma proteoglycan. The reactivity of PG-H to MO-225 is not affected by keratanase digestion but is completely abolished after chondroitinase digestion. Competitive binding analyses with various glycosaminoglycan samples indicate that the determinant recognized by MO-225 resides in a D-glucuronic acid 2-sulfate(beta 1----3)N-acetylgalactosamine 6-sulfate disaccharide unit (D-unit) common to antigenic chondroitin sulfates. A tetrasaccharide trisulfate containing D-unit at the reducing end is the smallest chondroitin sulfate fragment that can inhibit the binding of the antibody to PG-H. Decreasing the size of a D-unit-rich chondroitin sulfate by hyaluronidase digestion results in progressive reduction in its inhibitory activity. The results suggest that the epitope has a requirement for a long stretch of a disaccharide-repeating structure for a better fit to the antibody.
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PMID:A monoclonal antibody that specifically recognizes a glucuronic acid 2-sulfate-containing determinant in intact chondroitin sulfate chain. 243 33

The effects of steroid hormones on the synthesis of lactosaminoglycan (LAG)-containing oligosaccharides by mouse uteri are reported. The uterine LAG-containing oligosaccharides were degraded partially by Pseudomonas endo-beta-galactosidase, releasing an oligosaccharide of the apparent structure: Gal beta----N-acetylglucosaminyl(----N-acetylgalactosaminyl)beta 1,3----galactose. A larger fraction of the LAG-containing oligosaccharides bound to pokeweed mitogen than to Datura stramonium lectin, suggesting the presence of highly branched structures. LAG-containing oligosaccharides were resistant to sequential digestion with Pronase, nitrous acid, hyaluronidase, and chondroitinase ABC. These polysaccharides exhibited a Gal:GlcNAc:GalNAc ratio of approximately 1.0:1.0:0.3 and were not fucosylated. The ion-exchange behavior of the LAG-containing oligosaccharides before and after mild acid hydrolysis indicated the presence of sialic acid residues. The LAG-containing glycopeptides were highly resistant to beta-elimination but were released quantitatively by hydrazinolysis, demonstrating an N-linkage to protein. Binding to pokeweed mitogen was markedly enhanced following release of these oligosaccharides from peptides by hydrazinolysis, suggesting that peptide-bound oligosaccharides were partially inaccessible to the lectin. Molecular exclusion chromatography of the oligosaccharides released by hydrazinolysis revealed a broad distribution ranging from Mr 4,000 to 15,000 with a median Mr of approximately 8,000. We extended the above observations by determining how the steroid hormones 17-beta-estradiol (E2) and progesterone affected synthesis of the LAG-containing oligosaccharides in ovariectomized mice. Generally, E2 and a number of E2 agonists stimulated glycoconjugate synthesis; however, chronic E2 treatment or combined treatment with E2 plus progesterone caused the synthesis of most glycosaminoglycans to return to basal levels. In contrast, E2 either alone or in combination with progesterone stimulated synthesis of LAG-containing oligosaccharides in preference not only to glycosaminoglycans but also to other classes of N-linked oligosaccharides. This effect was apparent during both priming and nidatory E2 treatments. Collectively, these data provide the first demonstration of LAG-containing oligosaccharides in uteri and for the hormonally regulated synthesis of lactosaminoglycans. In addition, this is the first demonstration of the ability of steroid hormones to induce the synthesis of certain types of N-linked oligosaccharides in preference to others in the same tissue.
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PMID:Estrogen preferentially stimulates lactosaminoglycan-containing oligosaccharide synthesis in mouse uteri. 312 90

Nonsulfated, monosulfated, and disulfated glycopeptides containing the entire carbohydrate sequence of the glycosaminoglycan-specific linkage region were isolated after exhaustive enzymatic digestions of Swarm rat chondrosarcoma proteoglycans with chondroitinase ABC, papain, and Pronase. Their structures were examined by 500 MHz 1H NMR spectroscopy. The nonsulfated compound has the following structure with trace amounts of a few additional amino acids: delta 4,5-GlcA beta 1-3GalNAc beta 1-4GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl beta 1-O-Ser. The monosulfated compound has an ester sulfate on C-4 of the GalNAc residue and the disulfated compound has an additional hitherto unrecognized ester sulfate on C-4 of the second galactose residue which is remote from the innermost xylose. This new structure was confirmed by two-dimensional homonuclear Hartmann-Hahn spectroscopy. The molar ratio of the isolated nonsulfated, monosulfated, and disulfated compounds was 53:37:10 based on the serine contents. Biological significance of the newly found sulfated linkage structure is discussed.
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PMID:Structural studies on sulfated glycopeptides from the carbohydrate-protein linkage region of chondroitin 4-sulfate proteoglycans of swarm rat chondrosarcoma. Demonstration of the structure Gal(4-O-sulfate)beta 1-3Gal beta 1-4XYL beta 1-O-Ser. 313 45

Inter-alpha-trypsin inhibitor (ITI) in human plasma has a unique structural architecture composed of three polypeptide chains (H1, H2 and L chains), which are linked to each other through a chondroitin 4-sulphate chain. The structure of the carbohydrate-protein linkage region of the chondroitin 4-sulphate chain attached to the L chain was investigated. The peptide-chondroitin sulphate fraction was isolated by anion-exchange chromatography after exhaustive digestion with lysyl endopeptidase and then V8 protease. The chondroitin 4-sulphate chain was released from the peptides by beta-elimination using NaB3H4 and then digested with chondroitinase ABC. These treatments resulted in a single 3H-labelled hexasaccharide alditol fraction derived from the linkage region which had been associated with the L chain. Chemical and enzymatic analyses as well as fast-atom bombardment-mass spectrometry (FAB-MS) analysis revealed that the 3H-labelled hexasaccharide alditol had the following structure: delta HexA-alpha 1-3GalNAc(4-sulphate)beta 1-4GlcA beta 1-3Gal(4-sulphate)beta 1-3Gal beta 1-4Xyl-ol (where delta HexA is 4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid and Xyl-ol is xylitol). The structure contained the novel 4-sulphated Gal residue, which was previously demonstrated in a linkage hexasaccharide isolated from chondroitin 4-sulphate of rat chondrosarcoma (Sugahara et al., J. Biol. Chem., 263, 10168-10174, 1988) and of whale cartilage (Sugahara et al., Eur. J. Biochem., 202, 805-811, 1991). The above disulphated hexasaccharide alditol was the only component detected in the linkage region fraction of the chondroitin 4-sulphate chain of ITI, which implies some biological significance of this novel structure.
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PMID:The sulphated carbohydrate-protein linkage region isolated from chondroitin 4-sulphate chains of inter-alpha-trypsin inhibitor in human plasma. 754 56

The carbohydrate-protein linkage region of a chondroitin 4-sulfate chain attached to urinary trypsin inhibitor (UTI) was isolated from human urine and characterized structurally. The chondroitin 4-sulfate chain was released from UTI by beta-elimination using alkaline NaBH4 then digested with chondroitinase ABC. These treatments resulted in only a single hexasaccharide alditol derived from the carbohydrate-protein linkage region. Chemical and enzymic analyses and 600-MHz 1H-NMR spectroscopy revealed that the hexasaccharide alditol had the following structure: delta HexA alpha 1-3GalNAc(4-sulfate) beta 1-4GlcA beta 1- 3Gal(4-sulfate) beta 1-3Gal beta 1-4Xyl-ol, where delta HexA, GlcA and Xyl-ol represent 4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid, D-glucuronic acid and D-xylitol, respectively. This structure contained the novel 4-sulfated Gal residue, which was first demonstrated in one of the three linkage hexasaccharide-serines isolated from chondroitin 4-sulfate of rat chondrosarcoma [Sugahara, K., Yamashina, I., de Waard, P., Van Halbeek, H. & Vliegenhart, J. F. G. (1988) J. Biol. Chem. 263, 10168-10174]. This disulfated structure was recently identified as the sole structural component in the linkage hexasaccharide alditol fraction isolated from inter-alpha-trypsin inhibitor (ITI) in human plasma [Yamada, S., Oyama, M., Kinugasa, H., Nakagawa, T., Kawasaki, T., Nagasawa, S., Khoo, K.-H., Morris, H.R., Dell, A. & Sugahara, K. (1995) Glycobiology 5, 335-341]. The structural uniformity in the linkage hexasaccharide structure of ITI and UTI is in marked contrast to the heterogeneity demonstrated in the linkage hexasaccharides isolated from cartilaginous chondroitin sulfate whose linkage regions are sometimes but not always phosphorylated on the Xyl residue or sulfated on the Gal residue(s). The uniform structure containing the novel 4-sulfated Gal residue in the linkage region of UTI and ITI may imply its significance in the biosynthetic mechanism of chondroitin sulfate.
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PMID:The uniform galactose 4-sulfate structure in the carbohydrate-protein linkage region of human urinary trypsin inhibitor. 758 18


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