GlcNAcβ1→2Manα1→3(GlcNAcβ1→2Manα1→6)Manβ1→4GlcNAcβ1→4GlcNAcβ1-N-Ac | 1391912-81-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: GlcNAcβ1→2Manα1→3(GlcNAcβ1→2Manα1→6)Manβ1→4GlcNAcβ1→4GlcNAcβ1-N-Ac
• CAS: 1391912-81-4
• 化学式: C₅₂H₈₇N₅O₃₆
• 分子量: 1358.27
• InChiKey: ZFVVCJBEMPTZSJ-RLDNIBKKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -15.56
• 重原子数：
  93.0
• 可旋转键数：
  24.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  629.63
• 氢给体数：
  23.0
• 氢受体数：
  36.0

反应信息

• 作为反应物：
  描述：

  GlcNAcβ1→2Manα1→3(GlcNAcβ1→2Manα1→6)Manβ1→4GlcNAcβ1→4GlcNAcβ1-N-Ac 、 5`-二磷酸鸟嘌呤核苷-岩藻糖二钠盐 在 alkaline phosphatase from calf intestine 、 recombinant human α-1,6-fucosyltransferase 、 bovine serum albumin 作用下， 以 aq. buffer 为溶剂， 生成 GlcNAcβ1→2Manα1→3(GlcNAcβ1→2Manα1→6)Manβ1→4GlcNAcβ1→4GlcNAcβ1-N-Ac 、 鸟苷-5’-二磷酸
  参考文献：
  名称：

  Donor substrate binding and enzymatic mechanism of human core α1,6-fucosyltransferase (FUT8)

  摘要：

  Background: Fucosylation is essential for various biological processes including tumorigenesis, inflammation, cell-cell recognition and host-pathogen interactions. Biosynthesis of fucosylated glycans is accomplished by fucosyltransferases. The enzymatic product of core alpha 1,6-fucosyltransferase (FUT8) plays a major role in a plethora of pathological conditions, e.g. in prognosis of hepatocellular carcinoma and in colon cancer. Detailed knowledge of the binding mode of its substrates is required for the design of molecules that can modulate the activity of the enzyme.Methods: We provide a detailed description of binding interactions of human FUT8 with its natural donor substrate GDP-fucose and related compounds. GDP-Fuc was placed in FUT8 by structural analogy to the structure of protein-O-fucosyltransferase (cePOFUT) co-crystallized with GDP-Fuc. The epitope of the donor substrate bound to FUT8 was determined by STD NMR. The in silico model is further supported by experimental data from SPR binding assays. The complex was optimized by molecular dynamics simulations.Results: Guanine is specifically recognized by His363 and Asp453. Furthermore, the pyrophosphate is tightly bound via numerous hydrogen bonds and contributes affinity to a major part. Arg365 was found to bind both the beta-phosphate and the fucose moiety at the same time.Conclusions: Discovery of a novel structural analogy between cePOFUT and FUT8 allows the placement of the donor substrate GDP-Fuc. The positioning was confirmed by various experimental and computational techniques.General significance: The model illustrates details of the molecular basis of substrate recognition for a human fucosyltransferase for the first time and, thus, provides a basis for structure-based design of inhibitors. (C) 2012 Published by Elsevier B.V.

  DOI：

  10.1016/j.bbagen.2012.08.018