HEMAGGLUTININS FROM 2 INFLUENZA-VIRUS VARIANTS BIND TO SIALIC-ACID DERIVATIVES WITH MILLIMOLAR DISSOCIATION-CONSTANTS - A 500-MHZ PROTON NUCLEAR MAGNETIC-RESONANCE STUDY
HEMAGGLUTININS FROM 2 INFLUENZA-VIRUS VARIANTS BIND TO SIALIC-ACID DERIVATIVES WITH MILLIMOLAR DISSOCIATION-CONSTANTS - A 500-MHZ PROTON NUCLEAR MAGNETIC-RESONANCE STUDY
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DOI：
10.1021/bi00447a018
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发表时间：
1989-10-17
期刊：
影响因子：
2.9
通讯作者：
WILEY, DC
中科院分区：
文献类型：
--
作者：
SAUTER, NK;BEDNARSKI, MD;WILEY, DC
用核磁共振（NMR）光谱法测定流感病毒血凝素与其细胞表面配体唾液酸衍生物的平衡结合。通过观察蛋白质存在下唾液酸共振的扰动来定量结合。观察到的主要扰动是N-乙酰基甲基共振的化学位移，可能是由于甲基gorup接近色氨酸153。X-31血凝素结合甲基α-葡聚糖。解离常数为2.8mM的唾液酸糖苷，并且不与甲基β-葡萄糖苷结合。糖苷用乙酰基取代唾液酸的4-羟基几乎没有影响，而用乙酰基取代7-羟基阻止结合。用唾液酸化低聚糖进行的实验证实了文献报道的氨基酸226处的突变改变了血凝素对α的特异性。（2，6）和α.（2，3）糖苷键。唾液酸低聚糖的NMR谱线增宽表明唾液酸是与蛋白质接触的唯一组分。含有两个唾液酸残基的磷脂似乎有两种不同的结合模式。已经经历低pH诱导的构象变化的血凝素保留结合唾液酸的能力。
The equilibrium binding of influenza virus hemagglutinin to derivatives of its cell-surface ligand, sialic acid, was measured by nuclear magnetic resonance (NMR) spectroscooy. Binding was quantified by observing perturbations of sialic acid resonances in the presence of protein. The major pertubation observed was a chemical shift of the N-acetyl methyl resonance, persumably due to the proximity of the methyl gorup to tryptophan 153. X-31 hemagglutinin binds to the methyl .alpha.-glycoside of sialic acid with a dissociation constant of 2.8 mM and does not bind to the methyl .beta.-glycoside. Replacing the 4-hydroxyl group of sialic acid with an acetyl group has little effect, while replacing the 7-hydroxyl group with an acetyl prevents binding. Experiments with sialylated oligosaccharides confirm literature reports that mutations at amino acid 226 change the specificity of hemagglutinin for .alpha.(2,6) and .alpha.(2,3) glycosidic linkages. The NMR line broadening of sialyloligosaccharides suggests that sialic acid is the only component that contacts the protein. Saccharides containing two sialic acid residues appear to hve two separate binding modes. Hemagglutinin that has undergone a low pH induced conformational change retains the ability to bind sialic acid.