The Galβ-(syn)-gauche configuration is required for galectin-recognition disaccharides
The Galβ-(syn)-gauche configuration is required for galectin-recognition disaccharides
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DOI：
10.1016/j.bbagen.2011.04.001
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发表时间：
2011-07-01
影响因子：
3
通讯作者：
Hirabayashi, Jun
中科院分区：
文献类型：
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作者：
Iwaki, Jun;Tateno, Hiroaki;Hirabayashi, Jun
背景资料：半乳糖凝集素形成动物凝集素的大家族，个体成员具有各种不同的碳水化合物识别结构域（CRD），负责广泛的生理现象。半乳糖凝集素的糖结合亲和力先前由我们使用具有相对小的组（即，41)低聚糖。然而，对半乳糖凝集素识别酶的一致性规则的全面理解仍然受到缺乏关于它们在解离常数（K-d）方面对更大的寡糖组的糖结合特异性的基础知识的阻碍。在本研究中，我们通过使用142种荧光标记的寡糖，从更系统的角度扩展了FAC分析，最初集中于功能性人半乳糖凝集素-1-9。结合特性进一步验证与11个非人半乳糖凝集素和13个非半乳糖凝集素Gal/GalNAc结合凝集素属于不同family.Results：经验[半乳糖赤道[规则半乳糖凝集素识别二糖是由我们目前的研究和以前的工作由他人。然而，该规则对于最近报道的线虫二糖“Gal β 1-4-L-Fuc”无效[Butschi等人，PLoS Pathog，2010; 6（1）：e1000717]，因为该糖苷键针对L-Fuc的“轴向”4-OH。在仔细重新考虑结构数据后，我们得出了半乳糖凝集素识别二糖的最终规则，迄今为止鉴定的所有半乳糖凝集素都符合该规则，即，在重新定义的构型“Gal beta-（syn）-gauche”下。该规则也完美地工作从其他类型的凝集素的分化半乳糖凝集素。一般意义：目前的尝试应该提供一个基础，以解决的糖密码之谜，以及开发治疗性抑制剂模仿半乳糖凝集素配体。(C)2011 Elsevier B. V.保留所有权利。
Background: Galectins form a large family of animal lectins, individual members having variously divergent carbohydrate-recognition domains (CRDs) responsible for extensive physiological phenomena. Sugar-binding affinities of galectins were previously investigated by us using frontal affinity chromatography (FAC) with a relatively small set (i.e., 41) of oligosaccharides. However, total understanding of a consensus rule for galectin-recognition saccharides is still hampered by the lack of fundamental knowledge about their sugar-binding specificity toward a much larger panel of oligosaccharides in terms of dissociation constant (K-d).Methods: In the present study, we extended a FAC analysis from a more systematic viewpoint by using 142 fluorescent-labeled oligosaccharides, initially with focus on functional human galectins-1-9. Binding characteristics were further validated with 11 non-human galectins and 13 non-galectin Gal/GalNAc-binding lectins belonging to different families.Results: An empirical [Gal-equatorial[ rule for galectin-recognition disaccharides was first derived by our present research and previous works by others. However, this rule was not valid for a recently reported nematode disaccharide, "Gal beta 1-4-L-Fuc" [Butschi et al. PLoS Pathog, 2010; 6(1):e1000717], because this glycosidic linkage was directed to 'axial' 4-OH of L-Fuc. After careful reconsideration of the structural data, we reached an ultimate rule of galectin-recognition disaccharides, which all of the galectins so far identified fulfilled, i.e., under the re-defined configuration "Gal beta-(syn)-gauche". The rule also worked perfectly for differentiation of galectins from other types of lectins.General significance: The present attempt should provide a basis to solve the riddle of the glyco-code as well as to develop therapeutic inhibitors mimicking galectin ligands. (C) 2011 Elsevier B.V. All rights reserved.