Concanavalin A distorts the β-GlcNAc-(1→2)-Man linkage of β-GlcNAc-(1→2)-α-Man-(1→3)-[β-GlcNAc-(1→2)-α-Man-(1→6)]-Man upon binding
Concanavalin A distorts the β-GlcNAc-(1→2)-Man linkage of β-GlcNAc-(1→2)-α-Man-(1→3)-[β-GlcNAc-(1→2)-α-Man-(1→6)]-Man upon binding
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DOI：
10.1093/glycob/8.2.173
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发表时间：
1998-02-01
期刊：
影响因子：
4.3
通讯作者：
Naismith, JH
中科院分区：
文献类型：
--
作者：
Moothoo, DN;Naismith, JH
蛋白质对碳水化合物的识别是许多生物过程中的关键事件。已知伴刀豆球蛋白A特异性识别N-连接寡糖的五糖核心（β-GlcNAc-（1-->2）-α-Man-（1-->3）-[β-GlcNAc-（1-->2）-α-Man-（1-->6）]- Man），K-a为1.41 × 10（6）M-1。我们已经确定了与β-GlcNAc-（1->2）-α-Man-（1->3）-[β-GlcNAc-（1->2）-α-Man-（1->6）]-Man结合至2.7埃的伴刀豆球蛋白A的结构。在八个亚基中的六个中，所有五个糖残基都有明确的密度和有序的结合位点。五糖在所有八个亚基中采用相同的构象。结合位点是蛋白质表面上连续延伸的裂缝。货车范德华相互作用和氢键将碳水化合物锚在蛋白质上。两个GlcNAc残基都与蛋白质接触。五糖的1->6臂上的GlcNAc形成特别广泛的接触，并包括两个氢键。1->3臂GlcNAc的结合位点的范围小得多。低聚糖识别Con A发生通过特定的蛋白质碳水化合物的相互作用，并不需要招聘的外源水分子。1->6臂上的β-GlcNAc-（1->2）-Man糖苷键PSI扭转角从溶液中观察到的扭转角旋转超过50度。这种旋转与单糖位点上相互作用的破坏相结合。我们认为单糖位点的不稳定性和构象应变降低了由1->6臂GlcNAc位点处的额外相互作用释放的自由能。
Carbohydrate recognition by proteins is a key event in many biological processes. Concanavalin A is known to specifically recognize the pentasaccharide core (beta-GlcNAc-(1-->2)-alpha-Man-(1-->3)-[beta-GlcNAc-(1-->2)-alpha-Man-(1-->6)]- Man) of N-linked oligosaccharides with a K-a of 1.41 x 10(6) M-1. We have determined the structure of concanavalin A bound to beta-GlcNAc-(1-->2)-alpha-Man-(1-->3)-[beta-GlcNAc-(1-->2)-alpha-Man- (1-->6)]-Man to 2.7 Angstrom. In six of eight subunits there is clear density for all five sugar residues and a well ordered binding site. The pentasaccharide adopts the same conformation in all eight subunits. The binding site is a continuous extended cleft on the surface of the protein. Van der Waals interactions and hydrogen bonds anchor the carbohydrate to the protein. Both GlcNAc residues contact the protein. The GlcNAc on the 1-->6 arm of the pentasaccharide makes particularly extensive contacts and including two hydrogen bonds. The binding site of the 1-->3 arm GlcNAc is much less extensive. Oligosaccharide recognition by Con A occurs through specific protein carbohydrate interactions and does not require recruitment of adventitious water molecules. The beta-GlcNAc-(1-->2)-Man glycosidic linkage PSI torsion angle on the 1-->6 arm is rotated by over 50 degrees from that observed in solution. This rotation is coupled to disruption of interactions at the monosaccharide site. We suggest destabilization of the monosaccharide site and the conformational strain reduces the free energy liberated by additional interactions at the 1-->6 arm GlcNAc site.