N-Acetyl-4-O-acetylneuraminate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-Acetyl-4-O-acetylneuraminate
• 英文别名: (2S,4S,5R,6R)-5-acetamido-4-acetyloxy-2-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylate
• 化学式: C13H20NO10-
• 分子量: 350.3
• InChiKey: LVBIMVQYUKOENY-XAGGSGLKSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -2.2
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  186
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  水 、 N-Acetyl-4-O-acetylneuraminate 生成 乙酸盐 、 氢(+1)阳离子 、 N-acetylneuraminic acid
  参考文献：
  名称：

  Structure of coronavirus hemagglutinin-esterase offers insight into corona and influenza virus evolution

  摘要：

  血凝集素酯酶（HE）是一类病毒包膜糖蛋白家族，通过作为凝集素和受体破坏酶（RDE）来介导可逆的附着到O-乙酰化唾液酸上。相关的HE存在于流感C、牛病毒和冠状病毒中，显然是相对较近的侧向基因转移事件的结果。在这里，我们报道了冠状病毒（CoV）HE与其受体的晶体结构。我们表明CoV HE起源于类流感C的HE融合蛋白（HEF）。在这个过程中，HE从三聚体转化为二聚体，而融合域的残留物则被适应为建立新的单体-单体接触。虽然RDE-乙酰酯酶结构域的结构设计保持不变，但HE受体结合域的重建程度如此之高，以至于配体现在以相反的方向结合。这是令人惊讶的，因为HEF位点的架构在流感A HA中保持不变，尽管在更大的进化距离上，存在受体特异性的转换和广泛的抗原变异。显然，HA和HEF受到比HE更严格的选择性约束，限制了它们探索替代的结合位点拓扑的能力。我们将CoV HE受体结合位点的可塑性归因于HE和其伴侣尖峰蛋白S之间功能冗余所赋予的进化灵活性。我们的发现提供了独特的洞见，揭示了独立蛋白质进化在病毒基因交换后的结构和功能后果，并为广谱抗病毒药物设计开辟了潜在途径。

  DOI：

  10.1073/pnas.0800502105
• 作为产物：
  描述：

  (2R)-N-[3-(2-acetylsulfanylethylimino)-3-oxidopropyl]-4-[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonatooxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-2-hydroxy-3,3-dimethylbutanimidate 、 N-acetylneuraminic acid 生成 coenzyme A 、 N-Acetyl-4-O-acetylneuraminate
  参考文献：
  名称：

  Schauer R., Hoppe Seylers Z Physiol Chem, 1970, 0018-4888, 749-58

  摘要：

  DOI：

文献信息

• Structural basis for ligand and substrate recognition by torovirus hemagglutinin esterases
  作者：Martijn A. Langereis、Qinghong Zeng、Gerrit J. Gerwig、Barbara Frey、Mark von Itzstein、Johannis P. Kamerling、Raoul J. de Groot、Eric G. Huizinga

  DOI：10.1073/pnas.0904266106

  日期：2009.9.15

  Hemagglutinin esterases (HEs), closely related envelope glycoproteins in influenza C and corona- and toroviruses, mediate reversible attachment to O -acetylated sialic acids (Sias). They do so by acting both as lectins and as receptor-destroying enzymes, functions exerted by separate protein domains. HE divergence was accompanied by changes in quaternary structure and in receptor and substrate specificity. The selective forces underlying HE diversity and the molecular basis for Sia specificity are poorly understood. Here we present crystal structures of porcine and bovine torovirus HEs in complex with receptor analogs. Torovirus HEs form homodimers with sialate- O -acetylesterase domains almost identical to corresponding domains in orthomyxo- and coronavirus HEs, but with unique lectin sites. Structure-guided biochemical analysis of the esterase domains revealed that a functionally, but not structurally conserved arginine–Sia carboxylate interaction is critical for the binding and positioning of glycosidically bound Sias in the catalytic pocket. Although essential for efficient de- O -acetylation of Sias, this interaction is not required for catalysis nor does it affect substrate specificity. In fact, the distinct preference of the porcine torovirus enzyme for 9-mono- over 7,9-di- O -acetylated Sias can be explained from a single-residue difference with HEs of more promiscuous specificity. Apparently, esterase and lectin pockets coevolved; also the porcine torovirus HE receptor-binding site seems to have been designed to use 9-mono- and exclude di- O -acetylated Sias, possibly as an adaptation to replication in swine. Our findings shed light on HE evolution and provide fundamental insight into mechanisms of substrate binding, substrate recognition, and receptor selection in this important class of virion proteins.

  血凝集素酯酶（HEs）是流感C病毒、冠状病毒和托罗病毒中密切相关的包膜糖蛋白，介导可逆地与O-乙酰化唾液酸（Sias）结合。它们既作为凝集素又作为受体破坏酶，这些功能由不同的蛋白质结构域发挥。HE的分化伴随着四聚体结构和受体和底物特异性的变化。HE多样性的选择性力量和Sia特异性的分子基础尚不清楚。在这里，我们展示了与受体类似物复合物中的猪和牛托罗病毒HE的晶体结构。托罗病毒HE形成同源二聚体，其唾液酸O-乙酰酰化酯酶结构域与正黏液病毒和冠状病毒HE中的相应结构域几乎完全相同，但具有独特的凝集素位点。结构导向的生化分析表明，功能上但不是结构上保守的精氨酸-Sia羧酸盐相互作用对于在催化口袋中结合和定位糖基化结合的Sias至关重要。尽管对于Sias的高效去乙酰化至关重要，但这种相互作用对于催化并不是必需的，也不会影响底物特异性。事实上，猪托罗病毒酶对于9-单-O-乙酰化Sias的独特偏好可以从具有更广泛特异性的HEs的单个残基差异中解释。显然，酯酶和凝集素口袋共同进化；此外，猪托罗病毒HE受体结合位点似乎被设计为使用9-单-O-乙酰化Sias并排除二-O-乙酰化Sias，可能是为了适应在猪中复制。我们的发现揭示了HE的进化，并为这一重要类别的病毒蛋白的底物结合、底物识别和受体选择机制提供了基本见解。
• The Murine Coronavirus Hemagglutinin-esterase Receptor-binding Site: A Major Shift in Ligand Specificity through Modest Changes in Architecture
  作者：Martijn A. Langereis、Qinghong Zeng、Balthasar Heesters、Eric G. Huizinga、Raoul J. de Groot

  DOI：10.1371/journal.ppat.1002492

  日期：——

  The hemagglutinin-esterases (HEs), envelope glycoproteins of corona-, toro- and orthomyxoviruses, mediate reversible virion attachment to O-acetylated sialic acids (O-Ac-Sias). They do so through concerted action of distinct receptor-binding (“lectin”) and receptor-destroying sialate O-acetylesterase (”esterase”) domains. Most HEs target 9-O-acetylated Sias. In one lineage of murine coronaviruses, however, HE esterase substrate and lectin ligand specificity changed dramatically as these viruses evolved to use 4-O-acetylated Sias instead. Here we present the crystal structure of the lectin domain of mouse hepatitis virus (MHV) strain S HE, resolved both in its native state and in complex with a receptor analogue. The data show that the shift from 9-O- to 4-O-Ac-Sia receptor usage primarily entailed a change in ligand binding topology and, surprisingly, only modest changes in receptor-binding site architecture. Our findings illustrate the ease with which viruses can change receptor-binding specificity with potential consequences for host-, organ and/or cell tropism, and for pathogenesis.

  血凝素-酯酶（HEs）是冠状病毒、圆环病毒和正粘病毒的包膜糖蛋白，可促使病毒颗粒与O-乙酰化唾液酸（O-Ac-Sias）发生可逆性附着。它们通过不同的受体结合（“凝集素”）和受体破坏唾液酸O-乙酰酯酶（“酯酶”）域的协同作用来实现这一目标。大多数HEs以9-O-乙酰化唾液酸为靶标。然而，在鼠冠状病毒的一个分支中，HE酯酶底物和凝集素配体的特异性发生了巨大变化，因为这些病毒进化为使用4-O-乙酰化唾液酸。在这里，我们展示了鼠肝炎病毒（MHV）株S HE的凝集素域的晶体结构，该结构在天然状态下以及与受体类似物的复合物中均得到解析。数据显示，从9-O-到4-O-Ac-Sia受体的使用转变主要涉及配体结合拓扑结构的改变，而令人惊讶的是，受体结合位点结构仅发生轻微变化。我们的发现表明，病毒可以轻松改变受体结合的特异性，从而对宿主、器官和/或细胞的趋性以及发病机制产生潜在影响。
• Activity of influenza C virus <i>O</i>-acetylesterase with <i>O</i>-acetyl-containing compounds
  作者：A Garcia-Sastre、E Villar、J C Manuguerra、C Hannoun、J A Cabezas

  DOI：10.1042/bj2730435

  日期：1991.1.15

  Influenza C virus (strain C/Johannesburg/1/66) was grown, harvested, purified and used as source for the enzyme O-acetylesterase (N-acyl-O-acetylneuraminate O-acetylhydrolase; EC 3.1.1.53). This activity was studied and characterized with regard to some new substrates. The pH optimum of the enzyme is around 7.6, its stability at different pH values shows a result similar to that of the pH optimum, and its activity is well maintained in the pH range from 7.0 to 8.5 (all these tests were performed with 4-nitrophenyl acetate as substrate). Remarkable differences were found in the values of both Km and Vmax, with the synthetic substrates 4-nitrophenyl acetate, 2-nitrophenyl acetate, 4-methylumbelliferyl acetate, 1-naphthyl acetate and fluorescein diacetate. The use of 4-nitrophenyl acetate, 4-methylumbelliferyl acetate or 1-naphthyl acetate as substrate seems to be convenient for routine work, but it is better to carry out the measurements in parallel with those on bovine submandibular gland mucin (the latter is a natural and commercially available substrate). It was found that 4-acetoxybenzoic acid, as well as the methyl ester of 2-acetoxybenzoic acid, but not 2-acetoxybenzoic acid itself, are cleaved by this enzyme. Triacetin, di-O-acetyladenosine, tri-O-acetyladenosine, and di-O-acetyl-N-acetyladenosine phosphate, hitherto unreported as substrates for this viral esterase, are hydrolysed at different rates by this enzyme. We conclude that the O-acetylesterase from influenza C virus has a broad specificity towards both synthetic and natural non-sialic acid-containing substrates. Zn2+, Mn2+ and Pb2+ (as their chloride salts), N-acetylneuraminic acid, 4-methyl-umbelliferone and 2-acetoxybenzoic acid (acetylsalicylic acid) did not act as inhibitors.

  流感病毒C（菌株C/Johannesburg/1/66）被培养、收获、纯化并用作酶O-乙酰酰胺酯酶（N-酰-O-乙酰神经酰胺酸酯酰水解酶；EC 3.1.1.53）的来源。该活性被研究并对一些新底物进行了表征。该酶的pH最适值约为7.6，其在不同pH值下的稳定性显示出与pH最适值类似的结果，并且其活性在pH 7.0至8.5的范围内保持良好（所有这些测试都是以4-硝基苯酸酯为底物进行的）。在合成底物4-硝基苯酸酯、2-硝基苯酸酯、4-甲基翁贝利菲尔酸酯、1-萘酸酯和荧光素二乙酸酯的值中发现了显着的Km和Vmax差异。以4-硝基苯酸酯、4-甲基翁贝利菲尔酸酯或1-萘酸酯为底物似乎是方便的例行工作，但最好与牛颏下腺粘液（后者是一种天然且商业可得的底物）并行进行测量。发现4-乙酰氧基苯甲酸以及2-乙酰氧基苯甲酸的甲酯，但不是2-乙酰氧基苯甲酸本身，都被该酶切割。迄今为止未报告的三乙酸甘油酯、二-O-乙酰腺苷、三-O-乙酰腺苷和二-O-乙酰-N-乙酰腺苷磷酸作为该病毒酯酶的底物以不同的速率被水解。我们得出结论：来自流感病毒C的O-乙酰酰胺酯酶对合成和天然非唾液酸含量的底物具有广泛的特异性。Zn2+、Mn2+和Pb2+（作为其氯化物盐）、N-乙酰神经酰胺酸、4-甲基翁贝利菲隆和2-乙酰氧基苯甲酸（阿司匹林）均未作为抑制剂起作用。
• Schauer R., Hoppe Seylers Z Physiol Chem, 1970, 0018-4888, 595-602
  作者：Schauer R.

  DOI：——

  日期：——