The human ABO(H) blood group A- and B-synthesizing glycosyltransferases GTA and GTB have been structurally characterized to high resolution in complex with their respective trisaccharide antigen products. These findings are particularly timely and relevant given the dearth of glycosyltransferase structures collected in complex with their saccharide reaction products. GTA and GTB utilize the same acceptor substrates, oligosaccharides terminating with α-l-Fucp-(1→2)-β-d-Galp-OR (where R is a glycolipid or glycoprotein), but use distinct UDP donor sugars, UDP-N-acetylgalactosamine and UDP-galactose, to generate the blood group A (α-l-Fucp-(1→2)[α-d-GalNAcp-(1→3)]-β-d-Galp-OR) and blood group B (α-l-Fucp-(1→2)[α-d-Galp-(1→3)]-β-d-Galp-OR) determinant structures, respectively. Structures of GTA and GTB in complex with their respective trisaccharide products reveal a conflict between the transferred sugar monosaccharide and the β-phosphate of the UDP donor. Mapping of the binding epitopes by saturation transfer difference NMR measurements yielded data consistent with the X-ray structural results. Taken together these data suggest a mechanism of product release where monosaccharide transfer to the H-antigen acceptor induces active site disorder and ejection of the UDP leaving group prior to trisaccharide egress.

中文翻译：

---

与三糖反应产物复合的人类ABO（H）血型糖基转移酶的高分辨率晶体结构和STD NMR谱图表明产物释放的分子基础

人ABO（H）血型的A和B合成糖基转移酶GTA和GTB在结构上已与各自的三糖抗原产物形成了复杂的高分辨率结构。考虑到缺乏与它们的糖反应产物复合收集的糖基转移酶结构，这些发现是特别及时和相关的。GTA和GTB利用相同的受体底物，寡糖α-终止升-fUC p - （1→2）-β- d -Gal P-O R（其中R是糖脂或糖蛋白），但使用不同的供体的UDP糖，UDP - ñ -acetylgalactosamine和UDP-半乳糖，来生成血型A（α-升-fUC p - （1→2）[α-d -GalNAc p-（1→3）]-β- d -Gal p -OR）和血型B（α- 1- Fuc p-（1→2）[α- d -Gal p-（1→3） ）]-β- d -Gal p-OR）行列式结构。GTA和GTB与它们各自的三糖产物复合的结构揭示了转移的糖单糖与UDP供体的β-磷酸盐之间存在冲突。通过饱和转移差NMR测量对结合表位的作图产生了与X射线结构结果一致的数据。这些数据加在一起表明了产物释放的机制，其中单糖转移至H抗原受体诱导了活性位点紊乱和UDP离开基团在三糖流出之前的排出。