The antithrombin-binding sequence in heparin. Identification of an essential 6-O-sulfate group.
نویسندگان
چکیده
An octasaccharide with high affinity for antithrombin, isolated after partial deaminative cleavage of heparin, was previously found to have an L-iduronosyl-N-acetylglucosaminyl-6-O-sulfate nonreducing terminal disaccharide unit. After digestion of this octasaccharide with alpha-L-iduronidase and N-acetylglucosamine-6-sulfate sulfatase, two fractions, with high and low affinity for antithrombin, respectively, were isolated by affinity chromatography on antithrombin-Sepharose. Structural analysis showed that the high affinity fraction contained intact octasaccharide, whereas the low affinity fraction consisted of the expected heptasaccharide, lacking a 6-sulfate group on the terminal N-acetylglucosamine residue. Digestion of the octasaccharide with alpha-L-iduronidase only yielded heptasaccharide which was identical with the low affinity species except for the presence of this 6-sulfate group. This less degraded heptasaccharide retained high affinity for antithrombin. It is concluded that the 6-sulfate group on the N-acetylglucosamine residue is of critical importance to the interaction between heparin and antithrombin.
منابع مشابه
Extension and structural variability of the antithrombin-binding sequence in heparin.
Oligosaccharides with different affinities for antithrombin were isolated following partial deaminative cleavage of pig mucosal heparin with nitrous acid. The smallest high-affinity component obtained was previously identified as an octasaccharide with the predominant structure: (Formula: see text). The interaction of this octasaccharide, and of deca- and dodecasaccharides containing the same o...
متن کاملAn unusual antithrombin-binding heparin octasaccharide with an additional 3-O-sulfated glucosamine in the active pentasaccharide sequence.
The 3-O-sulfation of N-sulfated glucosamine is the last event in the biosynthesis of heparin/heparan sulfate, giving rise to the antithrombin-binding pentasaccharide sequence AGA*IA, which is largely associated with the antithrombotic activity of these molecules. The aim of the present study was the structural and biochemical characterization of a previously unreported AGA*IA*-containing octasa...
متن کاملLocation of antithrombin-binding regions in rat skin heparin proteoglycans.
Rat skin heparin proteoglycan labelled biosynthetically with 35S was fractionated on a column of antithrombin-Sepharose into fractions with varying degrees of affinity for antithrombin. These were treated with NaOH to release heparin chains (Mr 60,000-100,000), by beta-elimination or incubated with serum to produce fragments of the same order of size as commercial heparin (Mr 5000-30,000), by e...
متن کاملSequencing of 3-O sulfate containing heparin decasaccharides with a partial antithrombin III binding site.
Heparin- and heparan sulfate-like glycosaminoglycans (HLGAGs) represent an important class of molecules that interact with and modulate the activity of growth factors, enzymes, and morphogens. Of the many biological functions for this class of molecules, one of its most important functions is its interaction with antithrombin III (AT-III). AT-III binding to a specific heparin pentasaccharide se...
متن کاملStructural studies on the bacterial lyase-resistant tetrasaccharides derived from the antithrombin III-binding site of porcine intestinal heparin.
Three discrete tetrasaccharide structures which are resistant to Flavobacterium heparinase and heparitinases I and II were isolated from porcine intestinal heparin after exhaustive digestion with a mixture of all the above enzymes, and the tri-, tetra-, and penta-sulfated structures were determined by negative ion mode fast atom bombardment mass spectrometry and 500-MHz 1H NMR analysis as delta...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Journal of biological chemistry
دوره 258 16 شماره
صفحات -
تاریخ انتشار 1983