Ahmed H, Gabius H J
Max-Planck-Institut für Experimentelle Medizin, Göttingen, Federal Republic of Germany.
J Biol Chem. 1989 Nov 5;264(31):18673-8.
A Ca2+-independent sialic acid-specific lectin from two developmental stages of human placenta was similarly purified to apparent homogeneity by DEAE-cellulose chromatography, affinity chromatography on bovine submaxillary mucin, and gel filtration. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration disclosed a molecular mass of 53 kDa. The specificity of the lectin for O-acetylsialic acids was substantiated by the dependence of hemagglutination on the presence of acetylated sialic acids on the surface of mammalian erythrocytes of various sources, by hapten inhibition in hemagglutination assays with protease-treated rabbit erythrocytes and by hapten inhibition of binding of labeled N-acetylneuraminic acid-bovine serum albumin to the lectin in a solid-phase assay. Bovine and equine submaxillary mucins that contain 9(7,8)-O-acetyl and 4-O-acetylsialic acids were potent inhibitors in contrast to the non-acetylated sialic acids of ovine submaxillary mucin. Absence of inhibitory efficiency of other negatively charged substances like phosphorylated sugars, glucuronic acid, heparin, or oligodeoxynucleotides emphasized the importance of structural features instead of simple ionic interaction. In the presence of acetylation, the pattern of inhibition by gangliosides in the solid-phase assay indicated a preference to alpha-2,8- or alpha-2,6-linked sialic acids in comparison to alpha-2,3-linked moieties. Chemical modification of the lectin by group-specific reagents allowed to emphasize the role of primarily lysine residues, but also, although less pronounced, arginine, tryptophan, and carboxyl groups for ligand binding and/or maintenance of the active conformational state. Application of reagents, specific for histidine or tyrosine residues, failed to affect lectin activity.
从人胎盘两个发育阶段提取的一种不依赖钙离子的唾液酸特异性凝集素,通过DEAE - 纤维素色谱法、牛颌下粘蛋白亲和色谱法和凝胶过滤法,同样被纯化至表观均一。十二烷基硫酸钠 - 聚丙烯酰胺凝胶电泳和凝胶过滤显示其分子量为53 kDa。凝集素对O - 乙酰唾液酸的特异性通过以下几点得到证实:血凝反应依赖于各种来源哺乳动物红细胞表面乙酰化唾液酸的存在;用蛋白酶处理的兔红细胞进行血凝试验时的半抗原抑制作用;以及在固相试验中半抗原对标记的N - 乙酰神经氨酸 - 牛血清白蛋白与凝集素结合的抑制作用。含有9(7,8) - O - 乙酰基和4 - O - 乙酰基唾液酸的牛和马颌下粘蛋白是有效的抑制剂,而羊颌下粘蛋白的非乙酰化唾液酸则不然。其他带负电荷的物质如磷酸化糖、葡萄糖醛酸、肝素或寡脱氧核苷酸缺乏抑制效率,这强调了结构特征而非简单离子相互作用的重要性。在乙酰化存在的情况下,固相试验中神经节苷脂的抑制模式表明,与α - 2,3连接部分相比,其更倾向于α - 2,8或α - 2,6连接的唾液酸。用基团特异性试剂对凝集素进行化学修饰,可以突出主要是赖氨酸残基的作用,但精氨酸、色氨酸和羧基对配体结合和/或活性构象状态的维持也有作用,尽管作用较小。应用对组氨酸或酪氨酸残基特异的试剂未能影响凝集素活性。