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| Subject | Predicate | Object |
|---|---|---|
| http://purl.uniprot.org/citations/1939083 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/1939083 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/1939083 | http://www.w3.org/2000/01/rdf-schema#comment | "Heparin cofactor II (HCII) is a glycoprotein in human plasma that inhibits thrombin and chymotrypsin. Inhibition occurs when the protease attacks the reactive site peptide bond in HCII (Leu444-Ser445) and becomes trapped as a covalent 1:1 complex. Dermatan sulfate and heparin increase the rate of inhibition of thrombin, but not of chymotrypsin, greater than 1000-fold. The N-terminal portion of HCII contains two acidic repeats (Glu56-Asp-Asp-Asp-Tyr-Leu-Asp and Glu69-Asp-Asp-Asp-Tyr-Ile-Asp) that may bind to anion-binding exosite I of thrombin to facilitate covalent complex formation. To examine the importance of the acidic domain, we have constructed a series of 5' deletions in the HCII cDNA and expressed the recombinant HCII (rHCII) in Escherichia coli. Apparent second-order rate constants (k2) for inhibition of alpha-thrombin and chymotrypsin by each variant were determined. Deletion of amino acid residues 1-74 had no effect on the rate of inhibition of alpha-thrombin or chymotrypsin in the absence of a glycosaminoglycan. Similarly, the rate of inhibition of alpha-thrombin in the presence of a glycosaminoglycan was unaffected by deletion of residues 1-52. However, deletion of residues 1-67 (first acidic repeat) or 1-74 (first and second acidic repeats) greatly decreased the rate of inhibition of alpha-thrombin in the presence of heparin, dermatan sulfate, or a dermatan sulfate hexasaccharide that comprises the minimum high-affinity binding site for HCII. Deletion of one or both of the acidic repeats increased the apparent affinity of rHCII for heparin-Sepharose, suggesting that the acidic domain may interact with the glycosaminoglycan-binding site of native rHCII. The stimulatory effect of glycosaminoglycans on native rHCII was decreased by a C-terminal hirudin peptide which binds to anion-binding exosite I of alpha-thrombin. Furthermore, the ability of native rHCII to inhibit gamma-thrombin, which lacks the binding site for hirudin, was stimulated weakly by glycosaminoglycans. These results support a model in which the stimulatory effect of glycosaminoglycans on the inhibition of alpha-thrombin is mediated, in part, by the N-terminal acidic domain of HCII."xsd:string |
| http://purl.uniprot.org/citations/1939083 | http://purl.org/dc/terms/identifier | "doi:10.1016/s0021-9258(18)54913-9"xsd:string |
| http://purl.uniprot.org/citations/1939083 | http://purl.org/dc/terms/identifier | "doi:10.1016/s0021-9258(18)54913-9"xsd:string |
| http://purl.uniprot.org/citations/1939083 | http://purl.uniprot.org/core/author | "Tollefsen D.M."xsd:string |
| http://purl.uniprot.org/citations/1939083 | http://purl.uniprot.org/core/author | "Tollefsen D.M."xsd:string |
| http://purl.uniprot.org/citations/1939083 | http://purl.uniprot.org/core/author | "van Deerlin V.M.D."xsd:string |
| http://purl.uniprot.org/citations/1939083 | http://purl.uniprot.org/core/author | "van Deerlin V.M.D."xsd:string |
| http://purl.uniprot.org/citations/1939083 | http://purl.uniprot.org/core/date | "1991"xsd:gYear |
| http://purl.uniprot.org/citations/1939083 | http://purl.uniprot.org/core/date | "1991"xsd:gYear |
| http://purl.uniprot.org/citations/1939083 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/1939083 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/1939083 | http://purl.uniprot.org/core/pages | "20223-20231"xsd:string |
| http://purl.uniprot.org/citations/1939083 | http://purl.uniprot.org/core/pages | "20223-20231"xsd:string |
| http://purl.uniprot.org/citations/1939083 | http://purl.uniprot.org/core/title | "The N-terminal acidic domain of heparin cofactor II mediates the inhibition of alpha-thrombin in the presence of glycosaminoglycans."xsd:string |
| http://purl.uniprot.org/citations/1939083 | http://purl.uniprot.org/core/title | "The N-terminal acidic domain of heparin cofactor II mediates the inhibition of alpha-thrombin in the presence of glycosaminoglycans."xsd:string |
| http://purl.uniprot.org/citations/1939083 | http://purl.uniprot.org/core/volume | "266"xsd:string |
| http://purl.uniprot.org/citations/1939083 | http://purl.uniprot.org/core/volume | "266"xsd:string |
| http://purl.uniprot.org/citations/1939083 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/1939083 |
| http://purl.uniprot.org/citations/1939083 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/1939083 |
| http://purl.uniprot.org/citations/1939083 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/1939083 |
| http://purl.uniprot.org/citations/1939083 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/1939083 |
| http://purl.uniprot.org/uniprot/P05546 | http://purl.uniprot.org/core/citation | http://purl.uniprot.org/citations/1939083 |
| http://purl.uniprot.org/uniprot/P05546#attribution-6A4137F156D5F23F89B87711DAB1F29B | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/1939083 |