(2S)-2-amino-3-[hydroxy(oxido)phosphoryl]oxypropanoate

• 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: (2S)-2-amino-3-[hydroxy(oxido)phosphoryl]oxypropanoate
• 化学式: C₃H₆NO₆P
• 分子量: 183.058
• InChiKey: BZQFBWGGLXLEPQ-REOHCLBHSA-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：

  C-terminal Gly-NH-CH(2)-C(O)SH residue 、 (2S)-2-amino-3-[hydroxy(oxido)phosphoryl]oxypropanoate 生成 C-terminal Gly-NH-CH(2)-C(O)S-L-Cys 、 H3PO4
  参考文献：
  名称：

  结核分枝杆菌的半胱氨酸合酶（CysM）是O-磷酸丝氨酸巯基化酶：分枝杆菌中另一种半胱氨酸生物合成途径的证据。

  摘要：

  半胱氨酸的生物合成是至关重要的代谢途径，不仅为蛋白质从头合成提供了基础，而且作为氧化防御机制的一个组成部分，还原的硫醇在结核分枝杆菌的休眠状态下显得尤为重要。我们在这里显示，与以前的注释相反，半胱氨酸合酶CysM是O-磷酸丝氨酸特异性半胱氨酸合酶。CysM属于II型折叠的吡5醛5'-磷酸依赖性酶，如在2.1埃分辨率下确定的晶体结构所揭示。与酶结合的O-磷酸丝氨酸的模型表明，Arg220侧链与磷酸基团的氢键相互作用是底物选择性的关键特征。该残基的替换导致对O-磷酸丝氨酸的特异性显着丧失。尤其，与硫供体的反应不受氨基酸置换的影响。CysM对O-磷酸丝氨酸的特异性以及先前确立的通过硫代羧化CysO传递硫的新模式（Burns，KE，Baumgart，S.，Dorrestein，PC，Zhai，H.，McLafferty，FW和Begley，TP（2005） J. Am。Chem。Soc。127，1

  DOI：

  10.1074/jbc.m804877200
• 作为产物：
  描述：

  (S)-2-tert-Butoxycarbonylamino-3-{[2-(2-tert-butoxy-ethylsulfanyl)-ethoxy]-hydroxy-phosphoryloxy}-propionic acid tert-butyl ester 在 三氟乙酸 作用下， 反应 2.0h， 生成 硫二甘醇 、 (2S)-2-amino-3-[hydroxy(oxido)phosphoryl]oxypropanoate
  参考文献：
  名称：

  Solid phase synthesis of peptides containing a phosphoserine - sulfur mustard adduct

  摘要：

  Solid phase synthesis of peptides containing a serine thiodiglycol phosphate residue has been achieved by following a global on-resin phosphorylation strategy with a functionalized benzyl phosphoramidite. To preclude cleavage of the acid labile thiodiglycol phosphate ester during deprotection, the thioether functionality was temporarily protected as a sulfoxide. Copyright (C) 1996 Elsevier Science Ltd.

  DOI：

  10.1016/0960-894x(96)00357-5

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。
• Synthesis of L-2,3-Diaminopropionic Acid, a Siderophore and Antibiotic Precursor
  作者：Marek J. Kobylarz、Jason C. Grigg、Shin-ichi J. Takayama、Dushyant K. Rai、David E. Heinrichs、Michael E.P. Murphy

  DOI：10.1016/j.chembiol.2013.12.011

  日期：2014.3

  L-2,3-diaminopropionic acid (L-Dap) is an amino acid that is a precursor of antibiotics and staphyloferrin B a siderophore produced byStaphylococcus aureus. SbnA and SbnB are encoded by the staphyloferrin B biosynthetic gene cluster and are implicated in L-Dap biosynthesis. We demonstrate here that SbnA uses PLP and substratesO-phospho-L-serine and L-glutamate to produce a metaboliteN-(1-amino-1-c

  L-2,3-二氨基丙酸（L-Dap）是一种氨基酸，是抗生素的前体，而金黄色葡萄球菌B是一种由金黄色葡萄球菌产生的铁载体。SbnA和SbnB由葡萄铁蛋白B生物合成基因簇编码，并与L-Dap生物合成有关。我们在这里证明SbnA使用PLP和底物O-磷酸-L-丝氨酸和L-谷氨酸来生产代谢产物N-（1-氨基-1-羧基-2-乙基）-谷氨酸（ACEGA）。已显示SbnB使用NAD +氧化水解ACEGA，生成α-酮戊二酸酯和L-Dap。此外，我们描述了与NADH和ACEGA以及与NAD +和α-酮戊二酸酯复合的SbnB的晶体结构，以揭示底物结合，氧化和水解所需的残基。SbnA和SbnB有助于S的铁节约反应。
• 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。
• Characterization of a Novel Thermostable <i>O</i> -Acetylserine Sulfhydrylase from <i>Aeropyrum pernix</i> K1
  作者：Koshiki Mino、Kazuhiko Ishikawa

  DOI：10.1128/jb.185.7.2277-2284.2003

  日期：2003.4

  An O -acetylserine sulfhydrylase (OASS) from the hyperthermophilic archaeon Aeropyrum pernix K1, which shares the pyridoxal 5′-phosphate binding motif with both OASS and cystathionine β-synthase (CBS), was cloned and expressed by using Escherichia coli Rosetta(DE3). The purified protein was a dimer and contained pyridoxal 5′-phosphate. It was shown to be an enzyme with CBS activity as well as OASS activity in vitro. The enzyme retained 90% of its activity after a 6-h incubation at 100°C. In the O -acetyl- l -serine sulfhydrylation reaction, it had a pH optimum of 6.7, apparent K _m values for O -acetyl- l -serine and sulfide of 28 and below 0.2 mM, respectively, and a rate constant of 202 s ⁻¹ . In the l -cystathionine synthetic reaction, it showed a broad pH optimum in the range of 8.1 to 8.8, apparent K _m values for l -serine and l -homocysteine of 8 and 0.51 mM, respectively, and a rate constant of 0.7 s ⁻¹ . A. pernix OASS has a high activity in the l -cysteine desulfurization reaction, which produces sulfide and S -(2,3-hydroxy-4-thiobutyl)- l -cysteine from l -cysteine and dithiothreitol.

  摘要 一 O -乙酰丝氨酸巯基酶 (OASS) Aeropyrum pernix K1 与 OASS 和胱硫醚 β-合成酶（CBS）共享吡哆醛 5′-磷酸结合基团。 大肠杆菌 Rosetta(DE3)进行了克隆和表达。纯化的蛋白质为二聚体，含有 5′-磷酸吡哆醛。体外实验表明，它是一种具有 CBS 活性和 OASS 活性的酶。在 100 摄氏度下培养 6 小时后，该酶仍能保持 90% 的活性。在 O -乙酰- l -丝氨酸巯基化反应中，它的最适 pH 值为 6.7，明显的 K m 值为 O -乙酰基 l -丝氨酸和硫化物的值分别为 28 毫摩尔和低于 0.2 毫摩尔，速率常数为 202 秒 -1 .在 l 在 l-胞嘧啶合成反应中，它在 8.1 至 8.8 范围内显示出广泛的 pH 最适值，明显的 K m 值为 l -丝氨酸和 l -和 0.51 mM，速率常数为 0.7 s -1 . A. pernix OASS 在 l -半胱氨酸脱硫反应中具有很高的活性，该反应产生硫化物和 S -(2,3-hydroxy-4-thiobutyl)- l -从 l -半胱氨酸和二硫苏糖醇。
• A novel<i>O</i>-phospho-<scp>L</scp>-serine sulfhydrylation reaction catalyzed by<i>O</i>-acetylserine sulfhydrylase from<i>Aeropyrum pernix</i>K1
  作者：Koshiki Mino、Kazuhiko Ishikawa

  DOI：10.1016/s0014-5793(03)00913-x

  日期：2003.9.11

  O‐Acetylserine sulfhydrylase (OASS), a pyridoxal 5′‐phosphate (PLP)‐dependent enzyme, catalyzes the synthesis of L‐cysteine from O‐acetyl‐L‐serine and sulfide. O‐Acetyl‐L‐serine is labile at high temperatures at which hyperthermophilic archaea live. Herein, a study of the substrate specificity of OASS from Aeropyrum pernix K1 with respect to O‐acetyl‐L‐serine in L‐cysteine synthesis is described. L‐Azaserine, 3‐chloro‐L‐alanine, and O‐phospho‐L‐serine reacted with A. pernix OASS in a PLP‐dependent manner. Sulfhydrylation reactions using these substrates reached a maximum in the pH range between 7.3 and 8.1. L‐Azaserine and O‐phospho‐L‐serine were found to be heat‐stable substrates. The presence of FeCl3 or NiCl2 strongly inhibited the O‐acetyl‐L‐serine sulfhydrylation reaction, whereas the O‐phospho‐L‐serine sulfhydrylation reaction was only slightly inhibited. Kinetic analyses revealed that the O‐phospho‐L‐serine sulfhydrylation reaction as well as the O‐acetyl‐L‐serine sulfhydrylation reaction for A. pernix OASS followed a ping‐pong bi‐bi mechanism. In the case of the O‐phospho‐L‐serine sulfhydrylation reaction at 85°C, the K m values for O‐phospho‐L‐serine and sulfide, and the rate constant were 250 mM, 12.5 mM, and 14 000 s−1, respectively. The reactivity of O‐phospho‐L‐serine in the L‐cysteine synthetic reaction provides a key for understanding the biosynthesis of L‐cysteine by hyperthermophilic archaea. This is the first report of an enzyme that catalyzes the O‐phospho‐L‐serine sulfhydrylation reaction.

  O-乙酰丝氨酸硫水解酶（OASS）是一种依赖吡哆醛5′-磷酸（PLP）的酶，催化L-半胱氨酸从O-乙酰-L-丝氨酸和硫化物生成。O-乙酰-L-丝氨酸在高温下是不稳定的，而耐高温的嗜热古菌就生活在这样的高温环境中。本文描述了对南海永生菌（*Aeropyrum pernix*K1）的OASS对L-半胱氨酸合成过程中O-乙酰-L-丝氨酸的底物特异性的研究。L-甲丝氨酸、3-氯-L-丙氨酸和O-磷酸-L-丝氨酸均以依赖PLP的方式与南海永生菌的OASS反应。使用这些底物进行的硫水解反应在pH值为7.3至8.1之间达到最大值。L-甲丝氨酸和O-磷酸-L-丝氨酸被发现是耐热稳定的底物。FeCl3或NiCl2的加入强烈抑制了O-乙酰-L-丝氨酸的硫水解反应，然而O-磷酸-L-丝氨酸的硫水解反应仅有轻微抑制。动力学分析表明，O-磷酸-L-丝氨酸的硫水解反应以及南海永生菌OASS催化的O-乙酰-L-丝氨酸的硫水解反应均遵循ping-pong双分子机制。在85°C下，O-磷酸-L-丝氨酸的硫水解反应中，O-磷酸-L-丝氨酸和硫化物的Km值以及速率常数分别为250 mM、12.5 mM和14 000 s⁻¹。O-磷酸-L-丝氨酸在L-半胱氨酸合成反应中的反应活性为理解嗜热古菌L-半胱氨酸的生物合成提供了关键线索。这是首次报道能够催化O-磷酸-L-丝氨酸硫水解反应的酶。