GDP-6-deoxy-D-altrose | 1093679-47-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: GDP-6-deoxy-D-altrose
• 英文别名: GDP-6-deoxy-alpha-D-altrose；[[(2R,3S,4R,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3S,4R,5S,6R)-3,4,5-trihydroxy-6-methyloxan-2-yl] hydrogen phosphate
• CAS: 1093679-47-0
• 化学式: C₁₆H₂₅N₅O₁₅P₂
• 分子量: 589.347
• InChiKey: LQEBEXMHBLQMDB-AVOXIQDMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -6.6
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  307
• 氢给体数：
  9
• 氢受体数：
  16

反应信息

• 作为产物：
  描述：

  [(2S,3S,4R,5R)-5-(2-氨基-6-氧代-3H-嘌呤-9-基)-3,4-二羟基-四氢呋喃-2-基]甲氧基-[[(2R,3R,4S,6S)-3,4-二羟基-6-甲基-5-氧代-四氢吡喃-2-基]氧基-羟基-磷酰]氧基-次磷酸 在 GDP-L-fucose synthase Cys₁₀₉Ser mutant 、 重水 、 nicotinamide adenine dinucleotide 作用下， 反应 2.0h， 生成 GDP-6-deoxy-D-altrose 、 5`-二磷酸鸟嘌呤核苷-岩藻糖二钠盐
  参考文献：
  名称：

  Mechanism and Active Site Residues of GDP-Fucose Synthase

  摘要：

  L-Fucose, 6-deoxy-L-galactose, is a key component of many important glycoconjugates including the blood group antigens and the Lewis(x) ligands. The biosynthesis of GDP-L-fucose begins with the action of a dehydratase that converts GDP-D-mannose into GDP-4-keto-6-deoxy-mannose. The enzyme GDPfucose synthase, GFS, (also known as GDP-4-keto-6-deoxy-D-mannose epimerase/reductase, GMER) then converts GDP-4-keto-6-deoxy-D-mannose into GDP-L-fucose. The GFS reaction involves epimerizations at both C-3 '' and C-5 '' followed by an NADPH-dependent reduction of the carbonyl at C-4. This manuscript describes studies that elucidate the order of the epimerization steps and the roles of the active site acid/base residues responsible for the epimerizations. An active site mutant, Cys109Ser, produces GDP-6-deoxy-D-altrose as its major product indicating that C-3 '' epimerization occurs first and premature reduction of the GDP-4-keto-6-deoxy-D-altrose intermediate becomes competitive with GDP-L-fucose production. The same mutation results in the appearance of a kinetic isotope effect when [3 ''-H-2]-GDP-6-deoxy-4-keto-mannose is used as a substrate. This indicates that Cys109 is the base responsible for the deprotonation of the substrate at C-3 ''. The Cys109Ser mutant also catalyzes a rapid wash-in of solvent derived deuterium into the C-5 '' position of GDP-fucose in the presence of NADP(+). This confirms the order of epimerizations and the role of Cys109. Finally, the inactive His179Gln mutant readily catalyzes the wash-out of deuterium from the C-3 '' position of [3 ''-H-2]-GDP-6-deoxy-4-keto-mannose. Together these results strongly implicate an ordered sequence of epimerizations (C-3 '' followed by C-5 '') and suggest that Cys109 acts as a base and His179 acts as an acid in both epimerization steps.

  DOI：

  10.1021/ja807799k