alpha-D-Kdo-(2->4)-alpha-D-Kdo-(2->6)-lipid A 1-diphosphate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: alpha-D-Kdo-(2->4)-alpha-D-Kdo-(2->6)-lipid A 1-diphosphate
• 英文别名: (2R,4R,5R,6R)-2-[(2R,4R,5R,6R)-2-carboxylato-6-[(1R)-1,2-dihydroxyethyl]-2-[[(2R,3S,4R,5R,6R)-5-[[(3R)-3-dodecanoyloxytetradecanoyl]amino]-6-[[(2R,3S,4R,5R,6R)-3-hydroxy-5-[[(3R)-3-hydroxytetradecanoyl]amino]-4-[(3R)-3-hydroxytetradecanoyl]oxy-6-[oxido(phosphonatooxy)phosphoryl]oxyoxan-2-yl]methoxy]-3-phosphonatooxy-4-[(3R)-3-tetradecanoyloxytetradecanoyl]oxyoxan-2-yl]methoxy]-5-hydroxyoxan-4-yl]oxy-6-[(1R)-1,2-dihydroxyethyl]-4,5-dihydroxyoxane-2-carboxylate
• 化学式: C110H196N2O42P3-7
• 分子量: 2311.6
• InChiKey: FEIRMQZKCHCJCZ-OIPVZEHTSA-G

计算性质

• 辛醇/水分配系数(LogP)：
  22.5
• 重原子数：
  157
• 可旋转键数：
  96
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  705
• 氢给体数：
  12
• 氢受体数：
  42

反应信息

• 作为产物：
  描述：

  (2R,4R,5R,6R)-2-[(2R,4R,5R,6R)-2-carboxylato-6-[(1R)-1,2-dihydroxyethyl]-2-[[(2R,3S,4R,5R,6R)-5-[[(3R)-3-dodecanoyloxy-1-oxidotetradecylidene]amino]-6-[[(2R,3S,4R,5R,6R)-3-hydroxy-5-[[(3R)-3-hydroxy-1-oxidotetradecylidene]amino]-4-[(3R)-3-hydroxytetradecanoyl]oxy-6-phosphonooxyoxan-2-yl]methoxy]-3-phosphonatooxy-4-[(3R)-3-tetradecanoyloxytetradecanoyl]oxyoxan-2-yl]methoxy]-5-hydroxyoxan-4-yl]oxy-6-[(1R)-1,2-dihydroxyethyl]-4,5-dihydroxyoxane-2-carboxylate 、 C55 prenyl diphosphate 生成 alpha-D-Kdo-(2->4)-alpha-D-Kdo-(2->6)-lipid A 1-diphosphate 、 di-trans,octa-cis-Undecaprenyl phosphate
  参考文献：
  名称：

  脂质 A 的周质磷酸化与十一碳烯磷酸酯的合成有关。

  摘要：

  在大肠杆菌外膜中发现的脂质 A 的三分之一在位置 1（脂质 A 1-二磷酸）含有未取代的二磷酸单元。我们现在报告了一种内膜酶 LpxT (YeiU)，它专门将磷酸基团转移到脂质 A，形成 1-二磷酸物种。(32) 从 lpxT 突变体中获得的 P 标记的脂质 A 不产生脂质 A 1-二磷酸。以 Kdo(2)-[4'-(32)P]lipid A 作为受体的体外测定表明 LpxT 使用十一碳烯焦磷酸作为底物供体。通过用环状多肽抗生素杆菌肽螯合十一碳烯焦磷酸酯，证明了对野生型细菌中脂质 A 1-二磷酸酯形成的抑制，提供了十一碳烯焦磷酸酯作为整个细菌内的供体底物的证据。LpxT 催化的磷酸化依赖于脂质 A 通过 MsbA（一种脂质 A 翻转酶）穿过内膜的转运，表明存在周质活性位点。总之，我们展示了脂质 A 周质修饰的新途径，该途径与磷酸十一碳烯酯的合成直接相关，磷酸十一碳烯酯是合成各种细菌聚合物（如肽聚糖）所需的必需载体脂质。

  DOI：

  10.1111/j.1365-2958.2007.06044.x

文献信息

• Activation of PmrA inhibits LpxT-dependent phosphorylation of lipid A promoting resistance to antimicrobial peptides
  作者：Carmen M. Herrera、Jessica V. Hankins、M. Stephen Trent

  DOI：10.1111/j.1365-2958.2010.07150.x

  日期：——

  P>During its transport to the bacterial surface, the phosphate groups of the lipid A anchor of Escherichia coli and Salmonella lipopolysaccharide are modified by membrane enzymes including ArnT, EptA and LpxT. ArnT and EptA catalyse the periplasmic addition of the positively charged substituents 4-amino-4-deoxy-L-arabinose and phosphoethanolamine respectively. These modifications are controlled by the PmrA transcriptional regulator and confer resistance to cationic antimicrobial peptides, including polymyxin. LpxT, however, catalyses the phosphorylation of lipid A at the 1-position forming 1-diphosphate lipid A increasing the negative charge of the bacterial surface. Here, we report that PmrA is involved in the regulation of LpxT. Interestingly, this regulation does not occur at the level of transcription, but rather following the assembly of LpxT into the inner membrane. PmrA-dependent inhibition of LpxT is required for phosphoethanolamine decoration of lipid A, which is shown here to be critical for E. coli to resist the bactericidal activity of polymyxin. Furthermore, although Salmonella lipid A is more prevalently modified with l-4-aminoarabinose, we demonstrate that loss of Salmonella lpxT greatly increases EptA modification. The current work is an example of the complexities associated with the structural remodelling of Gram-negative lipopolysaccharides promoting bacterial survival.