O-phosphonatooxy-D-serine(2-)

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: O-phosphonatooxy-D-serine(2-)
• 英文别名: (2R)-2-azaniumyl-3-phosphonatooxypropanoate
• 化学式: C3H6NO6P-2
• 分子量: 183.06
• InChiKey: BZQFBWGGLXLEPQ-UWTATZPHSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  -4.7
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  140
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  水 、 O-phosphonatooxy-D-serine(2-) 生成 D-丝氨酸 、 H3PO4
  参考文献：
  名称：

  BeF\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy}\usepackage{mathrsfs}\setlength{\oddsidemargin}{-69pt}\begin{document}\begin{equation*}{\mathrm{_{3}^{-}}}\end{equation*}\end{document} acts as a phosphate analog in proteins phosphorylated on aspartate: Structure of a BeF\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy}\usepackage{mathrsfs}\setlength{\oddsidemargin}{-69pt}\begin{document}\begin{equation*}{\mathrm{_{3}^{-}}}\end{equation*}\end{document} complex with phosphoserine phosphatase

  摘要：

  蛋白质磷酸天冬氨酸键发挥着多种作用。在双组分信号转导系统的响应调节蛋白中，将天冬氨酸残基的磷酸化与从不活性构象转变为活性构象相耦合。在卤代酸脱卤酶（HAD）超家族的磷酸酶和突变酶中，磷酸天冬氨酸作为磷酸转移反应中的中间体，在P型ATP酶中，也是HAD家族的成员，它在化学能转化为离子梯度中起作用。在每种情况下，磷酸天冬氨酸键的不稳定性阻碍了对磷酸化形式的详细研究。对于响应调节蛋白，这一困难最近通过磷酸酯类似物BeF3-的使用得到了克服，它与其接收器结构域的活性位点天冬氨酸形成持久的复合物。我们现在通过解决BeF3-与甲烷菌PSP（磷酸丝氨酸磷酸酶）的复合物的1.5-A分辨率的X射线晶体结构来扩展这种类似物的应用于HAD超家族成员。该结构类似于磷酸酶中间体：BeF3-以磷酸酰基的四面体几何形状与Asp-11结合，与Mg2+配位，并与HAD超家族中保守的活性位点周围的残基结合。比较BeF3-·PSP和BeF3-·CeY（接收器结构域/响应调节蛋白）的活性位点揭示了惊人的相似性，这提供了对PSP和P型ATP酶功能的洞察。我们的结果表明，对于形成磷酸天冬氨酸键的蛋白质的结构研究，BeF3-的使用将远远超出响应调节蛋白的范围。

  DOI：

  10.1073/pnas.131213698

文献信息

• Panoramic view of a superfamily of phosphatases through substrate profiling
  作者：Hua Huang、Chetanya Pandya、Chunliang Liu、Nawar F. Al-Obaidi、Min Wang、Li Zheng、Sarah Toews Keating、Miyuki Aono、James D. Love、Brandon Evans、Ronald D. Seidel、Brandan S. Hillerich、Scott J. Garforth、Steven C. Almo、Patrick S. Mariano、Debra Dunaway-Mariano、Karen N. Allen、Jeremiah D. Farelli

  DOI：10.1073/pnas.1423570112

  日期：2015.4.21

  Here, we examine the activity profile of the haloalkanoic acid dehalogenase (HAD) superfamily by screening a customized library against >200 enzymes from a broad sampling of the superfamily. From this dataset, we can infer the function of nearly 35% of the superfamily. Overall, the superfamily was found to show high substrate ambiguity, with 75% of the superfamily utilizing greater than five substrates. In addition, the HAD members with the least amount of structural accessorization of the Rossmann fold were found to be the most specific, suggesting that elaboration of the core domain may have led to increased substrate range of the superfamily.

  这里，我们通过对一个定制库进行筛选，对来自广泛的HAD超家族样本中的200多种酶进行活性分析。从这组数据中，我们可以推断出几乎35%的超家族的功能。总体而言，发现超家族具有高度的底物模糊性，有75%的超家族利用了超过五种底物。此外，发现Rossmann折叠结构附件最少的HAD成员最为特定，这表明核心域的扩展可能导致了超家族底物范围的增加。
• Genome-wide Analysis of Substrate Specificities of the Escherichia coli Haloacid Dehalogenase-like Phosphatase Family
  作者：Ekaterina Kuznetsova、Michael Proudfoot、Claudio F. Gonzalez、Greg Brown、Marina V. Omelchenko、Ivan Borozan、Liran Carmel、Yuri I. Wolf、Hirotada Mori、Alexei V. Savchenko、Cheryl H. Arrowsmith、Eugene V. Koonin、Aled M. Edwards、Alexander F. Yakunin

  DOI：10.1074/jbc.m605449200

  日期：2006.11

  possess phosphatase, beta-phosphoglucomutase, phosphonatase, and dehalogenase activities. Using a representative set of 80 phosphorylated substrates, we characterized the substrate specificities of 23 soluble HADs encoded in the Escherichia coli genome. We identified small molecule phosphatase activity in 21 HADs and beta-phosphoglucomutase activity in one protein. The E. coli HAD phosphatases show high

  类卤酸脱卤酶（HAD）水解酶是一个庞大的超家族，主要由未鉴定的酶组成，少数成员显示具有磷酸酶，β-磷酸葡萄糖变位酶，磷酸酶和脱卤酶活性。我们使用一组代表性的80种磷酸化底物，对大肠杆菌基因组中编码的23种可溶性HAD的底物特异性进行了表征。我们确定了21种HADs中的小分子磷酸酶活性和一种蛋白质中的β-磷酸葡萄糖突变酶活性。大肠杆菌HAD磷酸酶显示出高催化效率和对广泛的磷酸化代谢产物的亲和力，这些代谢产物是各种代谢反应的中间产物。大多数E.coli HAD都没有遵循经典的“一种酶-一种底物”模型，而是显示出非常宽广且重叠的底物光谱。目前，至少有12种由HAD催化的反应未在酶命名法中分配EC号。出乎意料的是，大多数HAD水解了小的磷酸供体（乙酰磷酸酯，氨基甲酰磷酸酯和氨基磷酸酯），它们也用作两组分信号转导系统受体域自磷酸化的底物。对于一种HAD，YniC，在体内证实了磷酸酶活性与优选底物的生
• Structural Characterization of the Reaction Pathway in Phosphoserine Phosphatase: Crystallographic “snapshots” of Intermediate States
  作者：Weiru Wang、Ho S. Cho、Rosalind Kim、Jaru Jancarik、Hisao Yokota、Henry H. Nguyen、Igor V. Grigoriev、David E. Wemmer、Sung-Hou Kim

  DOI：10.1016/s0022-2836(02)00324-8

  日期：2002.5

  picture of the full reaction cycle. The structure of the apo state indicates partial unfolding of the enzyme to allow substrate binding, with refolding in the presence of substrate to provide specificity. Interdomain and active-site conformational changes are identified. The structure with the transition state analog bound indicates a "tight" intermediate. A striking structure homology, with significant

  磷酸丝氨酸磷酸酶（PSP）是一大类酶的成员，这些酶使用磷酸天冬氨酸-酶中间体催化磷酸酯水解。PSP可能是大脑中稳态d-丝氨酸水平的调节剂，它是N-甲基-d-天冬氨酸型谷氨酸受体的关键辅助激动剂。在这里，我们介绍了来自詹氏甲烷球菌的PSP的高分辨率（1.5-1.9 A）结构，该结构定义了底物结合之前的打开状态，结合了磷酸丝氨酸底物的复合物（在活性位点具有D到N突变），以及与AlF3的络合物，AlF3是反应中磷酸转移步骤的过渡态类似物。这些结构，以及针对BeF3-配合物（模仿磷酸酶）和在活性位点带有磷酸盐产物的酶所描述的结构，提供整个反应周期的详细结构图。载脂蛋白状态的结构指示酶的部分展开以允许底物结合，并且在存在底物的情况下重新折叠以提供特异性。域间和活动站点的构象变化被识别。具有过渡态模拟界的结构表示“紧密”中间体。PSP，P型ATP酶和响应调节剂之间具有显着的序列保守性，并且具有显着的序
• Characterization of M. tuberculosis SerB2, an Essential HAD-Family Phosphatase, Reveals Novel Properties
  作者：Gaya Prasad Yadav、Sonal Shree、Ruchi Maurya、Niyati Rai、Diwakar Kumar Singh、Kishore Kumar Srivastava、Ravishankar Ramachandran

  DOI：10.1371/journal.pone.0115409

  日期：——

  M. tuberculosis harbors an essential phosphoserine phosphatase (MtSerB2, Rv3042c) that contains two small- molecule binding ACT-domains (Pfam 01842) at the N-terminus followed by the phosphoserine phosphatase (PSP) domain. We found that exogenously added MtSerB2 elicits microtubule rearrangements in THP-1 cells. Mutational analysis demonstrates that phosphatase activity is co-related to the elicited rearrangements, while addition of the ACT-domains alone elicits no rearrangements. The enzyme is dimeric, exhibits divalent metal- ion dependency, and is more specific for l- phosphoserine unlike other classical PSPases. Binding of a variety of amino acids to the ACT-domains influences MtSerB2 activity by either acting as activators/inhibitors/have no effects. Additionally, reduced activity of the PSP domain can be enhanced by equimolar addition of the ACT domains. Further, we identified that G18 and G108 of the respective ACT-domains are necessary for ligand-binding and their mutations to G18A and G108A abolish the binding of ligands like l- serine. A specific transition to higher order oligomers is observed upon the addition of l- serine at ∼0.8 molar ratio as supported by Isothermal calorimetry and Size exclusion chromatography experiments. Mutational analysis shows that the transition is dependent on binding of l- serine to the ACT-domains. Furthermore, the higher-order oligomeric form of MtSerB2 is inactive, suggesting that its formation is a mechanism for feedback control of enzyme activity. Inhibition studies involving over eight inhibitors, MtSerB2, and the PSP domain respectively, suggests that targeting the ACT-domains can be an effective strategy for the development of inhibitors.

  结核杆菌携带一种重要的磷酸丝氨酸磷酸酶（MtSerB2，Rv3042c），它在 N 端含有两个小分子结合 ACT 域（Pfam 01842），其后是磷酸丝氨酸磷酸酶（PSP）域。我们发现，外源添加的 MtSerB2 会引起 THP-1 细胞中微管的重排。突变分析表明，磷酸酶活性与引起的重排有共同关系，而单独添加 ACT 域则不会引起重排。该酶是二聚体，表现出对二价金属离子的依赖性，而且与其他经典磷酸化酶不同，它对 l-磷酸丝氨酸更具特异性。多种氨基酸与 ACT 域的结合会影响 MtSerB2 的活性，既可能是激活剂，也可能是抑制剂，还可能没有任何影响。此外，等摩尔添加 ACT 结构域可增强 PSP 结构域降低的活性。此外，我们还发现各自 ACT 结构域中的 G18 和 G108 是配体结合所必需的，它们突变为 G18A 和 G108A 后，配体（如 l-丝氨酸）的结合就会消失。等温量热法和尺寸排阻色谱法实验证明，当加入摩尔比为 0.8 的 l-丝氨酸时，可以观察到向高阶低聚物的特定转变。突变分析表明，这种转变取决于 l-丝氨酸与 ACT 结构域的结合。此外，MtSerB2 的高阶寡聚形式没有活性，这表明它的形成是酶活性的一种反馈控制机制。分别涉及超过八种抑制剂、MtSerB2 和 PSP 结构域的抑制研究表明，靶向 ACT-结构域是开发抑制剂的有效策略。
• BeF\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy}\usepackage{mathrsfs}\setlength{\oddsidemargin}{-69pt}\begin{document}\begin{equation*}{\mathrm{_{3}^{-}}}\end{equation*}\end{document} acts as a phosphate analog in proteins phosphorylated on aspartate: Structure of a BeF\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy}\usepackage{mathrsfs}\setlength{\oddsidemargin}{-69pt}\begin{document}\begin{equation*}{\mathrm{_{3}^{-}}}\end{equation*}\end{document} complex with phosphoserine phosphatase
  作者：Ho Cho、Weiru Wang、Rosalind Kim、Hisao Yokota、Steven Damo、Sung-Hou Kim、David Wemmer、Sydney Kustu、Dalai Yan

  DOI：10.1073/pnas.131213698

  日期：2001.7.17

  Protein phosphoaspartate bonds play a variety of roles. In response regulator proteins of two-component signal transduction systems, phosphorylation of an aspartate residue is coupled to a change from an inactive to an active conformation. In phosphatases and mutases of the haloacid dehalogenase (HAD) superfamily, phosphoaspartate serves as an intermediate in phosphotransfer reactions, and in P-type ATPases, also members of the HAD family, it serves in the conversion of chemical energy to ion gradients. In each case, lability of the phosphoaspartate linkage has hampered a detailed study of the phosphorylated form. For response regulators, this difficulty was recently overcome with a phosphate analog, BeF \documentclass[12pt]minimal} \usepackageamsmath} \usepackagewasysym} \usepackageamsfonts} \usepackageamssymb} \usepackageamsbsy} \usepackagemathrsfs} \setlength\oddsidemargin}-69pt} \begindocument} \beginequation*}\mathrm_3}^-}}}\endequation*}\enddocument} , which yields persistent complexes with the active site aspartate of their receiver domains. We now extend the application of this analog to a HAD superfamily member by solving at 1.5-Å resolution the x-ray crystal structure of the complex of BeF \documentclass[12pt]minimal} \usepackageamsmath} \usepackagewasysym} \usepackageamsfonts} \usepackageamssymb} \usepackageamsbsy} \usepackagemathrsfs} \setlength\oddsidemargin}-69pt} \begindocument} \beginequation*}\mathrm_3}^-}}}\endequation*}\enddocument} with phosphoserine phosphatase (PSP) from Methanococcus jannaschii . The structure is comparable to that of a phosphoenzyme intermediate: BeF \documentclass[12pt]minimal} \usepackageamsmath} \usepackagewasysym} \usepackageamsfonts} \usepackageamssymb} \usepackageamsbsy} \usepackagemathrsfs} \setlength\oddsidemargin}-69pt} \begindocument} \beginequation*}\mathrm_3}^-}}}\endequation*}\enddocument} is bound to Asp-11 with the tetrahedral geometry of a phosphoryl group, is coordinated to Mg ²⁺ , and is bound to residues surrounding the active site that are conserved in the HAD superfamily. Comparison of the active sites of BeF \documentclass[12pt]minimal} \usepackageamsmath} \usepackagewasysym} \usepackageamsfonts} \usepackageamssymb} \usepackageamsbsy} \usepackagemathrsfs} \setlength\oddsidemargin}-69pt} \begindocument} \beginequation*}\mathrm_3}^-}}}\endequation*}\enddocument} ⋅PSP and BeF \documentclass[12pt]minimal} \usepackageamsmath} \usepackagewasysym} \usepackageamsfonts} \usepackageamssymb} \usepackageamsbsy} \usepackagemathrsfs} \setlength\oddsidemargin}-69pt} \begindocument} \beginequation*}\mathrm_3}^-}}}\endequation*}\enddocument} ⋅CeY, a receiver domain/response regulator, reveals striking similarities that provide insights into the function not only of PSP but also of P-type ATPases. Our results indicate that use of BeF \documentclass[12pt]minimal} \usepackageamsmath} \usepackagewasysym} \usepackageamsfonts} \usepackageamssymb} \usepackageamsbsy} \usepackagemathrsfs} \setlength\oddsidemargin}-69pt} \begindocument} \beginequation*}\mathrm_3}^-}}}\endequation*}\enddocument} for structural studies of proteins that form phosphoaspartate linkages will extend well beyond response regulators.

  蛋白质磷酸天冬氨酸键发挥着多种作用。在双组分信号转导系统的响应调节蛋白中，将天冬氨酸残基的磷酸化与从不活性构象转变为活性构象相耦合。在卤代酸脱卤酶（HAD）超家族的磷酸酶和突变酶中，磷酸天冬氨酸作为磷酸转移反应中的中间体，在P型ATP酶中，也是HAD家族的成员，它在化学能转化为离子梯度中起作用。在每种情况下，磷酸天冬氨酸键的不稳定性阻碍了对磷酸化形式的详细研究。对于响应调节蛋白，这一困难最近通过磷酸酯类似物BeF3-的使用得到了克服，它与其接收器结构域的活性位点天冬氨酸形成持久的复合物。我们现在通过解决BeF3-与甲烷菌PSP（磷酸丝氨酸磷酸酶）的复合物的1.5-A分辨率的X射线晶体结构来扩展这种类似物的应用于HAD超家族成员。该结构类似于磷酸酶中间体：BeF3-以磷酸酰基的四面体几何形状与Asp-11结合，与Mg2+配位，并与HAD超家族中保守的活性位点周围的残基结合。比较BeF3-·PSP和BeF3-·CeY（接收器结构域/响应调节蛋白）的活性位点揭示了惊人的相似性，这提供了对PSP和P型ATP酶功能的洞察。我们的结果表明，对于形成磷酸天冬氨酸键的蛋白质的结构研究，BeF3-的使用将远远超出响应调节蛋白的范围。