2-Aminoethyl hydrogen phosphate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磷酸及其衍生物
• 英文名称: 2-Aminoethyl hydrogen phosphate
• 化学式: C2H7NO4P-
• 分子量: 140.06
• InChiKey: SUHOOTKUPISOBE-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -4.9
• 重原子数：
  8
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  水 、 2-Aminoethyl hydrogen phosphate 生成 2-amino-ethanol; protonated form 、 H3PO4
  参考文献：
  名称：

  Comparative modelling of human PHOSPHO1 reveals a new group of phosphatases within the haloacid dehalogenase superfamily

  摘要：

  PHOSPHO1 是最近发现的一种磷酸酶，其表达在矿化细胞中上调，与基质矿化过程中无机磷酸盐的生成有关，这是骨骼发育的一个核心过程。该酶是依赖镁的水解酶卤酸脱卤酶（HAD）超家族的成员。然而，该酶的天然底物尚未确定，结构信息也尚不清楚。我们已经确定了一些物种中的同源蛋白，并根据梅氏球菌（Methanococcus jannaschii）磷酸丝氨酸磷酸酶（PSP）的晶体结构建立了人类 PHOSPHO1 的模型。该模型包括通过三个保守的 Asp 残基（Asp32、Asp34 和 Asp203）结合的催化 Mg2+ 原子；磷酸阴离子和两个水分子也提供了 O 配体。参与 PSP 催化水解的其他残基也是保守的，而且位于附近，这表明这两种酶具有相似的反应机制。在 PHOSPHO1 中，赋予该酶底物特异性的 PSP 残基（Arg56、Glu20、Met43 和 Phe49）都没有保守。相反，我们认为两个完全保守的 Asp 残基（Asp43 和 Asp123）不存在于 PSP 中，它们有助于 PHOSPHO1 的底物特异性。我们的研究结果表明，PHOSPHO1 不是 PSPs 亚家族的成员，而是属于 HAD 超家族中一个新的、密切相关的酶组。

  DOI：

  10.1093/protein/gzg126
• 作为产物：
  描述：

  a sphingoid 1-phosphate 生成 a fatty aldehyde 、 2-Aminoethyl hydrogen phosphate
  参考文献：
  名称：

  神经酰胺去饱和酶 FADS3 生物合成抗脂质微结构域鞘氨醇碱基 4,14-鞘氨醇

  摘要：

  鞘脂是多功能脂质。在鞘脂组分鞘氨醇碱基中，4,14-鞘氨醇 (SPD) 是独一无二的，它具有一个弯曲结构的顺式双键。尽管半个世纪前就发现了 SPD，但其组织分布、生物合成和降解仍知之甚少。在这里，我们建立了一种特异性和定量的 SPD 测量方法，发现 SPD 存在于广泛的哺乳动物组织中。SPD 在肾脏中特别丰富，其中 SPD 的量约为鞘氨醇的 2/3，鞘氨醇是哺乳动物中最丰富的鞘氨醇碱。尽管 SPD 代谢为神经酰胺和 SPD 1-磷酸酯的效率几乎与鞘氨醇相同，但它不太容易被裂解反应降解，至少在体外是这样。我们将脂肪酸去饱和酶家族蛋白 FADS3 鉴定为一种神经酰胺去饱和酶，它通过使含有鞘氨醇的神经酰胺去饱和来产生 SPD 神经酰胺。SPD 鞘脂优先定位于脂质微域之外，这表明 SPD 在脂质微域形成方面与其他鞘氨醇碱基相比具有不同的功能。总之，我们揭示了 SPD 的生物合成和降解途径及其特征性

  DOI：

  10.1096/fj.201902645r

文献信息

• Functional Characterization of Two PLP-Dependent Enzymes Involved in Capsular Polysaccharide Biosynthesis from <i>Campylobacter jejuni</i>
  作者：Alexander S. Riegert、Tamari Narindoshvili、Adriana Coricello、Nigel G. J. Richards、Frank M. Raushel

  DOI：10.1021/acs.biochem.1c00439

  日期：2021.9.21

  food-borne illness in the world, surpassing Salmonella and E. coli. Coating the surface of C. jejuni is a layer of sugar molecules known as the capsular polysaccharide that, in C. jejuni NCTC 11168, is composed of a repeating unit of d-glycero-l-gluco-heptose, d-glucuronic acid, d-N-acetyl-galactosamine, and d-ribose. The d-glucuronic acid moiety is further amidated with either serinol or ethanolamine

  空肠弯曲杆菌是一种革兰氏阴性病原菌，可引起弯曲杆菌病，一种肠胃炎。空肠弯曲菌是世界上食源性疾病的最常见原因，超过沙门氏菌和大肠杆菌。空肠弯曲杆菌表面包裹着一层称为荚膜多糖的糖分子，在空肠弯曲杆菌NCTC 11168 中，它由d-甘油-l-葡萄糖-庚糖、d-葡萄糖醛酸、d - N-乙酰-半乳糖胺和d-核糖。d _-葡萄糖醛酸部分进一步用丝氨醇或乙醇胺酰胺化。尚不清楚这些修饰是如何合成并附着在多糖上的。在这里，我们报告了来自空肠弯曲菌NCTC 11168的两种先前未表征的磷酸吡哆醛 (PLP) 依赖性酶 Cj1436 和 Cj1437 的催化活性。结合质谱和核磁共振，我们确定 Cj1436 催化脱羧L-丝氨酸磷酸盐到乙醇胺磷酸盐。Cj1437 显示在l存在下催化磷酸二羟丙酮转氨为 ( S )-丝氨醇磷酸盐-谷氨酸。讨论了最终形成空肠弯曲菌荚膜多糖中葡萄糖醛酸酰胺亚结构的可能途径。
• Differential Role of Human Choline Kinase α and β Enzymes in Lipid Metabolism: Implications in Cancer Onset and Treatment
  作者：David Gallego-Ortega、Ana Ramirez de Molina、Maria Angeles Ramos、Fatima Valdes-Mora、Maria Gonzalez Barderas、Jacinto Sarmentero-Estrada、Juan Carlos Lacal

  DOI：10.1371/journal.pone.0007819

  日期：——

  Background The Kennedy pathway generates phosphocoline and phosphoethanolamine through its two branches. Choline Kinase (ChoK) is the first enzyme of the Kennedy branch of synthesis of phosphocholine, the major component of the plasma membrane. ChoK family of proteins is composed by ChoKα and ChoKβ isoforms, the first one with two different variants of splicing. Recently ChoKα has been implicated in the carcinogenic process, since it is over-expressed in a variety of human cancers. However, no evidence for a role of ChoKβ in carcinogenesis has been reported. Methodology/Principal Findings Here we compare the in vitro and in vivo properties of ChoKα1 and ChoKβ in lipid metabolism, and their potential role in carcinogenesis. Both ChoKα1 and ChoKβ showed choline and ethanolamine kinase activities when assayed in cell extracts, though with different affinity for their substrates. However, they behave differentially when overexpressed in whole cells. Whereas ChoKβ display an ethanolamine kinase role, ChoKα1 present a dual choline/ethanolamine kinase role, suggesting the involvement of each ChoK isoform in distinct biochemical pathways under in vivo conditions. In addition, while overexpression of ChoKα1 is oncogenic when overexpressed in HEK293T or MDCK cells, ChoKβ overexpression is not sufficient to induce in vitro cell transformation nor in vivo tumor growth. Furthermore, a significant upregulation of ChoKα1 mRNA levels in a panel of breast and lung cancer cell lines was found, but no changes in ChoKβ mRNA levels were observed. Finally, MN58b, a previously described potent inhibitor of ChoK with in vivo antitumoral activity, shows more than 20-fold higher efficiency towards ChoKα1 than ChoKβ. Conclusion/Significance This study represents the first evidence of the distinct metabolic role of ChoKα and ChoKβ isoforms, suggesting different physiological roles and implications in human carcinogenesis. These findings constitute a step forward in the design of an antitumoral strategy based on ChoK inhibition.

  背景 肯尼迪途径通过其两个分支产生磷脂酰胆碱和磷脂酰乙醇胺。胆碱激酶（ChoK）是肯尼迪途径合成磷脂酰胆碱的第一种酶，磷脂酰胆碱是血浆膜的主要成分。胆碱激酶家族由ChoKα和ChoKβ同工型组成，前者有2种不同的剪接变体。最近，ChoKα被证实与致癌过程有关，因为它会在多种人类癌症中过度表达。然而，目前尚无证据表明ChoKβ在致癌过程中发挥作用。 方法/主要发现 在此，我们比较了ChoKα1和ChoKβ在脂质代谢中的体外和体内特性，以及它们在致癌过程中的潜在作用。在细胞提取物中检测时，ChoKα1和ChoKβ均表现出胆碱和乙醇胺激酶活性，尽管它们对底物的亲和力不同。然而，当它们在整细胞中过度表达时，它们的行为会有所不同。ChoKβ表现出乙醇胺激酶的作用，而ChoKα1则表现出胆碱/乙醇胺双激酶的作用，这表明在体内条件下，每种ChoK同工型都参与不同的生化途径。此外，当在HEK293T或MDCK细胞中过度表达ChoKα1时，它会产生致癌作用，而ChoKβ的过度表达则不足以诱导体外细胞转化或体内肿瘤生长
• Comparative modelling of human PHOSPHO1 reveals a new group of phosphatases within the haloacid dehalogenase superfamily
  作者：A. J. Stewart、R. Schmid、C. A. Blindauer、S. J. Paisey、C. Farquharson

  DOI：10.1093/protein/gzg126

  日期：2003.12.1

  PHOSPHO1 is a recently identified phosphatase whose expression is upregulated in mineralizing cells and is implicated in the generation of inorganic phosphate for matrix mineralization, a process central to skeletal development. The enzyme is a member of the haloacid dehalogenase (HAD) superfamily of magnesium‐dependent hydrolases. However, the natural substrate(s) is as yet unidentified and to date no structural information is known. We have identified homologous proteins in a number of species and have modelled human PHOSPHO1 based upon the crystal structure of phosphoserine phosphatase (PSP) from Methanococcus jannaschii. The model includes the catalytic Mg2+ atom bound via three conserved Asp residues (Asp32, Asp34 and Asp203); O‐ligands are also provided by a phosphate anion and two water molecules. Additional residues involved in PSP‐catalysed hydrolysis are conserved and are located nearby, suggesting both enzymes share a similar reaction mechanism. In PHOSPHO1, none of the PSP residues that confer the enzyme’s substrate specificity (Arg56, Glu20, Met43 and Phe49) are conserved. Instead, we propose that two fully conserved Asp residues (Asp43 and Asp123), not present in PSPs contribute to substrate specificity in PHOSPHO1. Our findings show that PHOSPHO1 is not a member of the subfamily of PSPs but belongs to a novel, closely related enzyme group within the HAD superfamily.

  PHOSPHO1 是最近发现的一种磷酸酶，其表达在矿化细胞中上调，与基质矿化过程中无机磷酸盐的生成有关，这是骨骼发育的一个核心过程。该酶是依赖镁的水解酶卤酸脱卤酶（HAD）超家族的成员。然而，该酶的天然底物尚未确定，结构信息也尚不清楚。我们已经确定了一些物种中的同源蛋白，并根据梅氏球菌（Methanococcus jannaschii）磷酸丝氨酸磷酸酶（PSP）的晶体结构建立了人类 PHOSPHO1 的模型。该模型包括通过三个保守的 Asp 残基（Asp32、Asp34 和 Asp203）结合的催化 Mg2+ 原子；磷酸阴离子和两个水分子也提供了 O 配体。参与 PSP 催化水解的其他残基也是保守的，而且位于附近，这表明这两种酶具有相似的反应机制。在 PHOSPHO1 中，赋予该酶底物特异性的 PSP 残基（Arg56、Glu20、Met43 和 Phe49）都没有保守。相反，我们认为两个完全保守的 Asp 残基（Asp43 和 Asp123）不存在于 PSP 中，它们有助于 PHOSPHO1 的底物特异性。我们的研究结果表明，PHOSPHO1 不是 PSPs 亚家族的成员，而是属于 HAD 超家族中一个新的、密切相关的酶组。
• Human PHOSPHO1 exhibits high specific phosphoethanolamine and phosphocholine phosphatase activities
  作者：Scott J. ROBERTS、Alan J. STEWART、Peter J. SADLER、Colin FARQUHARSON

  DOI：10.1042/bj20040511

  日期：2004.8.15

  Human PHOSPHO1 is a phosphatase enzyme for which expression is upregulated in mineralizing cells. This enzyme has been implicated in the generation of Pi for matrix mineralization, a process central to skeletal development. PHOSPHO1 is a member of the haloacid dehalogenase (HAD) superfamily of Mg2+-dependent hydrolases. However, substrates for PHOSPHO1 are, as yet, unidentified and little is known about its activity. We show here that PHOSPHO1 exhibits high specific activities toward phosphoethanolamine (PEA) and phosphocholine (PCho). Optimal enzymic activity was observed at approx. pH 6.7. The enzyme shows a high specific Mg2+-dependence, with apparent Km values of 3.0 μM for PEA and 11.4 μM for PCho. These results provide a novel mechanism for the generation of Pi in mineralizing cells from PEA and PCho.

  人类 PHOSPHO1 是一种在矿化细胞中表达上调的磷酸酶。这种酶与基质矿化所需的π的生成有关，而基质矿化是骨骼发育的核心过程。PHOSPHO1 是 Mg2+ 依赖性水解酶卤酸脱卤酶（HAD）超家族的成员。然而，PHOSPHO1 的底物尚未确定，对其活性也知之甚少。我们在这里发现，PHOSPHO1 对磷酸乙醇胺（PEA）和磷酸胆碱（PCho）具有很高的特异性活性。在 pH 值约为 6.7 时观察到了最佳的酶活性。该酶显示出高度的特异性 Mg2+ 依赖性，对 PEA 的表观 Km 值为 3.0 μM，对 PCho 的表观 Km 值为 11.4 μM。这些结果为矿化细胞中 PEA 和 PCho 产生 Pi 提供了一种新的机制。
• Microbial metabolism of amino alcohols. Metabolism of ethanolamine and 1-aminopropan-2-ol in species of <i>Erwinia</i> and the roles of amino alcohol kinase and amino alcohol <i>O</i>-phosphate phospho-lyase in aldehyde formation
  作者：Alan Jones、Anne Faulkner、John M. Turner

  DOI：10.1042/bj1340959

  日期：1973.8.1

  1. Growth of Erwinia carotovora N.C.P.P.B. 1280 on media containing 1-aminopropan-2-ol compounds or ethanolamine as the sole N source resulted in the excretion of propionaldehyde or acetaldehyde respectively. The inclusion of (NH4)2SO4 in media prevented aldehyde formation. 2. Growth, microrespirometric and enzymic evidence implicated amino alcohol O-phosphates as aldehyde precursors. An inducibly formed ATP–amino alcohol phosphotransferase was partially purified and found to be markedly stimulated by ADP, unaffected by NH4+ ions and more active with ethanolamine than with 1-aminopropan-2-ol compounds. Amino alcohol O-phosphates were deaminated by an inducible phospho-lyase to give the corresponding aldehydes. This enzyme, separated from the kinase during purification, was more active with ethanolamine O-phosphate than with 1-aminopropan-2-ol O-phosphates. Activity of the phospho-lyase was unaffected by a number of possible effectors, including NH4+ ions, but its formation was repressed by the addition of (NH4)2SO4 to growth media. 3. E. carotovora was unable to grow with ethanolamine or 1-aminopropan-2-ol compounds as sources of C, the production of aldehydes during utilization as N sources being attributable to the inability of the microbe to synthesize aldehyde dehydrogenase. 4. Of seven additional strains of Erwinia examined similar results were obtained only with Erwinia ananas (N.C.P.P.B. 441) and Erwinia milletiae (N.C.P.P.B. 955).

  1. 在含有1-氨基丙醇化合物或乙醇胺作为唯一氮源的培养基上生长的Erwinia carotovora N.C.P.P.B. 1280会分别分泌丙酮醛或乙醛。在培养基中加入（NH4）2SO4可以防止醛类物质的形成。 2. 生长、微量呼吸和酶学证据表明，氨基醇O-磷酸盐是醛类物质的前体。一种可诱导形成的ATP-氨基醇磷酸转移酶被部分纯化，并发现其受ADP显著刺激，不受NH4+离子影响，并且在乙醇胺比在1-氨基丙醇化合物中更活跃。氨基醇O-磷酸盐经可诱导的磷酸裂解酶脱氨基后生成相应的醛类物质。在纯化过程中与激酶分离的这种酶在乙醇胺O-磷酸盐中的活性比在1-氨基丙醇O-磷酸盐中更高。磷酸裂解酶的活性不受多种可能的影响因素（包括NH4+离子）的影响，但它的形成会受到在生长培养基中添加（NH4）2SO4的抑制。 3. E. carotovora无法利用乙醇胺或1-氨基丙醇化合物作为C源生长，利用作为N源时产生的醛类物质是由于微生物无法合成醛脱氢酶。 4. 对于另外七个Erwinia菌株的检查，只有Erwinia ananas（N.C.P.P.B. 441）和Erwinia milletiae（N.C.P.P.B. 955）得到了类似的结果。