EVALUATION OF CRITICAL GROUPS REQUIRED FOR THE BINDING OF HEPARIN TO ANTITHROMBIN
EVALUATION OF CRITICAL GROUPS REQUIRED FOR THE BINDING OF HEPARIN TO ANTITHROMBIN
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DOI：
10.1073/pnas.81.4.1030
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发表时间：
1984-01-01
期刊：
影响因子：
--
通讯作者：
ROSENBERG, RD
中科院分区：
文献类型：
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作者：
ATHA, DH;STEPHENS, AW;ROSENBERG, RD
猪粘膜肝素的八糖结构域的各种单糖残基的定量重要性，负责这种寡糖的结合，人和牛的抗凝血酶进行了检查。通过酶消化制备八糖的不同片段，并通过平衡透析测定这些寡糖对抗凝血酶的亲和力。非还原端和还原端四糖对八糖的结合能的贡献显然相等。非还原端四糖内的N-乙酰基葡糖胺部分的O 6-硫酸酯基团负责八糖结合能的45%。该残基侧翼的2个非硫酸化糖醛酸基团和该四糖序列还原端上的N-硫酸化葡糖胺残基（具有独特的O3-硫酸酯取代基）均不显著影响八糖的结合能。非还原端四糖内2个糖醛酸部分的硫酸化缺失可能是允许N-乙酰葡糖胺O 6-硫酸酯基团与抗凝血酶分子上的特定区域相互作用所必需的。不能排除O3-硫酸基团在非还原端四糖内的O 6-硫酸基团的定向中起重要作用的可能性。
The quantitative importance of various monosaccharide residues of an octasaccharide domain of porcine mucosal heparin that are responsible for the binding of this oligosaccharide to human and bovine antithrombin was examined. Different fragments of the octasaccharide were prepared by enzymatic digestion and the avidities of these oligoaccharides for antithrombin were determined by equilibrium dialysis. The non-reducing-end and the reducing-end tetrasaccharides evidently contribute equally to the binding energy of the octasaccharide. The O6-sulfate group of the N-acetyl glucosamine moiety within the nonreducing-end tetrasaccharide is responsible for .apprxeq. 45% of the binding energy of the octasaccharide. Neither the 2 non-sulfated uronic acid groups that flank this residue nor the N-sulfated glucosamine residue on the reducing end of this tetrasaccharide sequence that bears the unique O3-sulfate substituent contribute significantly to the binding energy of the octasaccharide. The lack of sulfation of the 2 uronic acid moieties within the nonreducing-end tetrasaccharide may be required to permit the N-acetyl glucosamne O6-sulfate group to interact with a specific region on the anti-thrombin molecule. The possibility that the O3-sulfate group plays an important role in orienting this O6-sulfate group within the nonreducing-end tetrasaccharide cannot be excluded.