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• W2054418617 endingPage "156" @default.
• W2054418617 startingPage "148" @default.
• W2054418617 abstract "A variety of sulphated polyanions in addition to heparin and dermatan sulphate stimulate the inhibition of thrombin by heparin cofactor II (HCII). Previous investigations indicated that the binding sites on HCII for heparin and dermatan sulphate overlap but are not identical. In this study we determined the concentrations (IC50) of various polyanions required to stimulate thrombin inhibition by native recombinant HCII in comparison with three recombinant HCII variants having decreased affinity for heparin (Lys-173-->Gln), dermatan sulphate (Arg-189-->His), or both heparin and dermatan sulphate (Lys-185-->Asn). Pentosan polysulphate, sulphated bis-lactobionic acid amide, and sulphated bis-maltobionic acid amide resembled dermatan sulphate, since their IC50 values were increased to a much greater degree (>/=8-fold) by the mutations Arg-189-->His and Lys-185-->Asn than by Lys-173-->Gln (</=1.5-fold). By contrast, the IC50 values for fucosylated chondroitin sulphate, chondroitin sulphate E, dextran sulphate, and fucoidan were minimally affected. Only in the case of heparin was the IC50 increased to a greater degree by both Lys-173-->Gln and Lys-185-->Asn (>/=6-fold) than by Arg-189-->His (</=1.5-fold). None of the polyanions significantly stimulated inhibition of thrombin by an N-terminal deletion mutant of HCII (Delta1-74). These results suggest that, like dermatan sulphate and heparin, other polyanions stimulate HCII primarily by an allosteric mechanism requiring the N-terminal acidic domain." @default.
• W2054418617 created "2016-06-24" @default.
• W2054418617 creator A5006916097 @default.
• W2054418617 creator A5020157694 @default.
• W2054418617 creator A5061002869 @default.
• W2054418617 date "1999-04-01" @default.
• W2054418617 modified "2023-09-23" @default.
• W2054418617 title "Amino acid residues of heparin cofactor II required for stimulation of thrombin inhibition by sulphated polyanions" @default.
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• W2054418617 doi "https://doi.org/10.1016/s0167-4838(99)00051-5" @default.
• W2054418617 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10209287" @default.
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