Differential recognition of the type I and IIH antigen acceptors by the human ABO(H) blood group A and B glycosyltransferases
Differential recognition of the type I and IIH antigen acceptors by the human ABO(H) blood group A and B glycosyltransferases
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DOI：
10.1074/jbc.m507620200
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发表时间：
2006-02-10
影响因子：
4.8
通讯作者：
Evans, SV
中科院分区：
文献类型：
--
作者：
Letts, JA;Rose, NL;Evans, SV
人ABO（H）血型A和B抗原由同源糖基转移酶A（GTA）和B（GTB）产生，其分别将单糖GalNAc和Gal添加到细胞表面H抗原。在糖基转移酶对一组对应于受体片段的底物的识别的第一次全面结构研究中，在对应于I型受体不同片段的寡糖存在下，已经确定了GTA和GTB的14种高分辨率晶体结构。（α-L-Fucp-（1 -> 2）-β-D-Galp-（1 -> 3）-β-D-GlcNAc β-OR，其中R是天然受体中的糖蛋白或糖脂）和II型（α-L-Fucp-（1 -> 2）-β-D-Galp-（1 -> 4）-β-D-GlcNAcp-OR）H抗原三联体。GTA和GTB仅在四个"关键"氨基酸残基（Arg/Gly-176、Gly/Ser-235、Leu/Met-266和Gly/Ala-268）上不同。由于这些酶都利用H抗原受体，四个关键残基被认为是严格参与供体识别;然而，我们现在报告说，受体结合和随后的转移显着影响这些残基中的两个：甘氨酸/丝氨酸-235和亮氨酸/蛋氨酸-266。此外，这些结构表明，受体识别是由中央半乳糖残基，尽管事实上，L-Fuc残基是需要有效的催化和GTA和GTB的模型抑制剂的设计直接洞察。
The human ABO( H) blood group A and B antigens are generated by the homologous glycosyltransferases A (GTA) and B (GTB), which add the monosaccharides GalNAc and Gal, respectively, to the cell-surface H antigens. In the first comprehensive structural study of the recognition by a glycosyltransferase of a panel of substrates corresponding to acceptor fragments, 14 high resolution crystal structures of GTA and GTB have been determined in the presence of oligosaccharides corresponding to different segments of the type I (alpha-L-Fucp-(1 -> 2)-beta-D-Galp-(1 -> 3)-beta-D-GlcNAcp-OR, where R is a glycoprotein or glycolipid in natural acceptors) and type II (alpha-L-Fucp-(1 -> 2)-beta-D-Galp-(1 -> 4)-beta-D-GlcNAcp-OR) H antigen trisaccharides. GTA and GTB differ in only four '' critical '' amino acid residues (Arg/Gly-176, Gly/Ser-235, Leu/Met-266, and Gly/Ala-268). As these enzymes both utilize the H antigen acceptors, the four critical residues had been thought to be involved strictly in donor recognition; however, we now report that acceptor binding and subsequent transfer are significantly influenced by two of these residues: Gly/Ser-235 and Leu/Met-266. Furthermore, these structures show that acceptor recognition is dominated by the central Gal residue despite the fact that the L-Fuc residue is required for efficient catalysis and give direct insight into the design of model inhibitors for GTA and GTB.