Showing papers by "James A. Huntington published in 1996"

Mechanism of Heparin Activation of Antithrombin. Evidence for Reactive Center Loop Preinsertion with Expulsion upon Heparin Binding

Abstract: A heparin-induced conformational change is required to convert antithrombin from a slow to a fast inhibitor of factor Xa. It has been proposed [van Boeckel et al. (1994) Nat. Struct. Biol. 1, 423−4...

Antithrombin-heparin affinity reduced by fucosylation of carbohydrate at asparagine 155.

Abstract: The two human plasma antithrombin isoforms, α and β, differ in glycosylation at asparagine 135. Only the α form carries carbohydrate at this position and has lower affinity for heparin than the β form. We previously found additional heterogeneity in a recombinant N135Q antithrombin variant, evidenced by two isoforms with a 2-fold difference in heparin affinity [Turko, I. V., Fan, B., & Gettins, P. G. W. (1993) FEBS Lett. 335, 9−12]. To test whether this heterogeneity of heparin affinity results from specific glycosylation differences, we have determined the carbohydrate composition at the three remaining glycosylation sites, asparagine residues 96, 155, and 192, in each of the two N135Q isoforms, by a combination of peptide fragmentation and electrospray mass spectrometry. Patterns of glycosylation at residues 96 and 192 were similar for each isoform and showed the presence of mono-, bi-, and triantennary complex carbohydrate, as well as fucosylation of all types of chains. At position 155, however, there...