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)

Increased storage of basic proline-rich secretory proteins induced in rat parotid acinar cells by isoproterenol is accompanied by increased storage of a chondroitin sulfate-containing proteoglycan. Amino acid analysis of the purified proteoglycan and the chondroitinase digestion products reveals that the polypeptide backbone is a proline-rich protein. Most sulfation occurs in Golgi elements; however, a small fraction of the proteoglycan can be labeled by incubating isolated secretion granules with [35S]phosphoadenosine phosphosulfate ([35S]PAPS), and the amount of sulfate incorporation decreases with increased granule maturity. In vitro incorporation is sensitive to inhibitors of PAPS transport and occurs in intact granules as shown by radioautography. Both the increased production of a chondroitin sulfate proteoglycan following isoproterenol treatment and its sulfation at sites of secretory condensation and storage suggest that sulfation may aid secretory packaging by reducing the known fixed positive charge that stems from the large concentration of basic secretory proteins.
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PMID:Proteoglycan sulfation and storage parallels storage of basic secretory proteins in exocrine cells. 195 74

Histidine-rich glycoprotein (HRG) is an alpha2-glycoprotein found in mammalian plasma at high concentrations (approximately 150 microg/ml) and is distinguished by its high content of histidine and proline. Structurally, HRG is a modular protein consisting of an N-terminal cystatin-like domain (N1N2), a central histidine-rich region (HRR) flanked by proline-rich sequences, and a C-terminal domain. HRG binds to cell surfaces and numerous ligands such as plasminogen, fibrinogen, thrombospondin, C1q, heparin, and IgG, suggesting that it may act as an adaptor protein either by targeting ligands to cell surfaces or by cross-linking soluble ligands. Despite the suggested functional importance of HRG, the cell-binding characteristics of the molecule are poorly defined. In this study, HRG was shown to bind to most cell lines in a Zn(2+)-dependent manner, but failed to interact with the Chinese hamster ovary cell line pgsA-745, which lacks cell-surface glycosaminoglycans (GAGs). Subsequent treatment of GAG-positive Chinese hamster ovary cells with mammalian heparanase or bacterial heparinase III, but not chondroitinase ABC, abolished HRG binding. Furthermore, blocking studies with various GAG species indicated that only heparin was a potent inhibitor of HRG binding. These data suggest that heparan sulfate is the predominate cell-surface ligand for HRG and that mammalian heparanase is a potential regulator of HRG binding. Using recombinant forms of full-length HRG and the N-terminal N1N2 domain, it was shown that the N1N2 domain bound specifically to immobilized heparin and cell-surface heparan sulfate. In contrast, synthetic peptides corresponding to the Zn(2+)-binding HRR of HRG did not interact with cells. Furthermore, the binding of full-length HRG, but not the N1N2 domain, was greatly potentiated by physiological concentrations of Zn2+. Based on these data, we propose that the N1N2 domain binds to cell-surface heparan sulfate and that the interaction of Zn2+ with the HRR can indirectly enhance cell-surface binding.
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PMID:Histidine-rich glycoprotein binds to cell-surface heparan sulfate via its N-terminal domain following Zn2+ chelation. 1513 72