Identification of preferred carbohydrate binding modes in xenoreactive antibodies by combining conformational filters and binding site maps
Identification of preferred carbohydrate binding modes in xenoreactive antibodies by combining conformational filters and binding site maps
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DOI：
10.1093/glycob/cwq022
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发表时间：
2010-06-01
期刊：
影响因子：
4.3
通讯作者：
Ramsland, Paul A.
中科院分区：
文献类型：
--
作者：
Agostino, Mark;Sandrin, Mauro S.;Ramsland, Paul A.
碳水化合物是出了名的柔性分子。然而，它们作为特定的配体在许多生化过程中起着重要的作用。因此，了解碳水化合物是如何被其他生物大分子(通常是蛋白质)识别的具有相当大的科学价值。干扰碳水化合物-蛋白质的相互作用在对抗一系列疾病状态方面是一种潜在有用的策略，在促进异体和异种移植方面也是至关重要的。我们设计了一种用于分析碳水化合物-蛋白质相互作用的电子方案。在这项研究中，我们应用该方案来确定与一组异种反应性抗体形成的复合体中的α-半乳糖终末糖类抗原的结构。结合模式的最重要特征是所有结合模式中Galβ(1，4)GLC/GlcNAc连接的固定构象。末端Galα(1，3)Gal连接的首选构象因抗体结合部位的地形而异，尽管一些所研究的抗体可能识别多个Galα(1，3)Gal构象。所获得的结合模式表明，每种抗体在识别靶抗原时使用不同的机制。
Carbohydrates are notoriously flexible molecules. However, they have an important role in many biochemical processes as specific ligands. Understanding how carbohydrates are recognized by other biological macromolecules (usually proteins) is therefore of considerable scientific value. Interfering with carbohydrate-protein interactions is a potentially useful strategy in combating a range of disease states, as well as being of critical importance in facilitating allo- and xenotransplantation. We have devised an in silico protocol for analyzing carbohydrate-protein interactions. In this study, we have applied the protocol to determine the structures of alpha Gal-terminating carbohydrate antigens in complex with a panel of xenoreactive antibodies. The most important feature of the binding modes is the fixed conformation of the Gal beta(1,4)Glc/GlcNAc linkage across all of the binding modes. The preferred conformation of the terminal Gal alpha(1,3)Gal linkage varies depending on the antibody binding site topography, although it is possible that some of the antibodies studied recognize more than one Gal alpha(1,3)Gal conformation. The binding modes obtained indicate that each antibody uses distinct mechanisms in recognizing the target antigens.