estrone-3-sulfate | 114697-37-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: estrone-3-sulfate
• 英文别名: estrone sulfate；oestrone sulphate；Estrone 3-sulfate；[(8R,9S,13S,14S)-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl] sulfate
• CAS: 114697-37-9
• 化学式: C₁₈H₂₁O₅S
• 分子量: 349.428
• InChiKey: JKKFKPJIXZFSSB-CBZIJGRNSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  91.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  estrone-3-sulfate 、 水 生成 雌酚酮 、 氢(+1)阳离子 、 硫酸酯
  参考文献：
  名称：

  Characterization of steroid sulfatase in the MC3T3-E1 mouse pre-osteoblastic cell line

  摘要：

  Regulation of bone density is partly dependent upon steroid hormones, with estrogens playing an important role. Inactive conjugated estrogens may serve as precursors to active estrogens, especially in post-menopausal women, via steroid sulfatase, which converts conjugated estrogens into unconjugated estrogens. The purpose of this study was to characterize steroid sulfatase in the MC3T3-E1 mouse pre-osteoblastic cell line. Enzyme conversion assays were performed on whole MC3T3-E1 cells in culture and on microsomes prepared by differential centrifugation. H-3-E1S and H-3-DHEAS were used as tracers. and radioinert E1S and DHEAS were used as substrate. Whole cells and microsomes exhibited steroid sulfatase activity, which was blocked by the specific inhibitor estrone-3-O-sulfamate (EMATE). The K-m of steroid sulfatase in microsomes averaged 83 mu M when using E1S as substrate and 64 mu M when using DHEAS. Western blotting of MC3T3-E1 microsomes for steroid sulfatase was performed, after SDS-PAGE, using an antibody generated against a peptide based on a conserved region of steroid sulfatase. Western blotting revealed three bands of cross-reactivity, ranging from 50 to 79 kDa. Reverse transcriptase polymerase chain reaction (RT-PCR), using specific primers, resulted in a single cDNA band of the expected size (100 bp) and sequence, indicating the presence of steroid sulfatase mRNA. Growth assays revealed that the MC3T3-E1 cells were stimulated by estradiol-17 beta, and also by estrone sulfate and DHEAS, revealing that the cells can use steroid sulfatase to produce active estrogens. Furthermore, growth of these cells in the presence of estradiol, estrone and estrone sulfate was inhibited by the estrogen receptor blocker ICI 182,780, indicating that stimulation of cell growth is mediated by the estrogen receptor. In our studies, four lines of evidence (enzyme activity, immunoassay, RT-PCR and growth assays) demonstrated the presence of steroid sulfatase in mouse MC3T3-E1 bone cells. The existence of steroid sulfatase in these pre-osteoblastic cells, along with the ability of sulfated steroids to promote their growth, suggest the possibility that this enzyme is involved in regulation of bone density in mice. (c) 2012 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2012.02.024
• 作为产物：
  描述：

  雌酚酮 在 咪唑 、 sodium methylate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 14.0h， 生成 estrone-3-sulfate
  参考文献：
  名称：

  Compositions and methods for sulfation of carbohydrates

  摘要：

  在某一方面，本公开涉及一种简便策略，用于向糖类、氨基酸及其他底物的硅化羟基引入电子缺乏的芳基硫酸二酯。通过选择性水解以及去除电子缺乏的芳香基团，可以高效生成硫酸化的糖类、肽类及其他化合物。在糖类、肽类等化合物的合成早期阶段引入电子缺乏的芳基硫酸二酯，如本公开所述，可以避免耗时的保护基操作，简化硫酸化产物的纯化过程，提高整体产率和效率。本摘要旨在作为特定领域中的检索工具，并不旨在限制本公开的内容。

  公开号：

  US11505568B1

文献信息

• Transition State of the Sulfuryl Transfer Reaction of Estrogen Sulfotransferase
  作者：Richard H. Hoff、Przemyslaw G. Czyryca、Meihao Sun、Thomas S. Leyh、Alvan C. Hengge

  DOI：10.1074/jbc.m604205200

  日期：2006.10

  Kinetic isotope effects have been measured for the estrogen sulfotransferase-catalyzed sulfuryl (SO3) transfer from p-nitrophenyl sulfate to the 5'-phosphoryl group of 3'-phosphoadenosine 5'-phosphate. 18(V/K)nonbridge = 1.0016 +/- 0.0005, 18(V/K)bridge = 1.0280 +/- 0.0006, and 15(V/K) = 1.0014 +/- 0.0004. (15(V/K) refers to the nitro group in p-nitrophenyl sulfate). The kinetic isotope effects indicate

  已测量了雌激素磺基转移酶催化的硫基（SO3）从对硝基苯基硫酸盐转移至3'-磷腺苷5'-磷酸的5'-磷酰基的动力学同位素效应。18（V / K）非桥= 1.0016 +/- 0.0005，18（V / K）桥= 1.0280 +/- 0.0006，15（V / K）= 1.0014 +/- 0.0004。（15（V / K）是指对硝基苯基硫酸盐中的硝基）。动力学同位素效应表明过渡态中大量的SO键裂变，离去基团被部分电荷中和。非桥基硫氧原子中的小动力学同位素效应表明，这些原子的键序未发生明显变化，这与适度的亲核参与一致。
• Structural and Chemical Profiling of the Human Cytosolic Sulfotransferases
  作者：Abdellah Allali-Hassani、Patricia W Pan、Ludmila Dombrovski、Rafael Najmanovich、Wolfram Tempel、Aiping Dong、Peter Loppnau、Fernando Martin、Janet Thonton、Aled M Edwards、Alexey Bochkarev、Alexander N Plotnikov、Masoud Vedadi、Cheryl H Arrowsmith

  DOI：10.1371/journal.pbio.0050097

  日期：——

  The human cytosolic sulfotransfases (hSULTs) comprise a family of 12 phase II enzymes involved in the metabolism of drugs and hormones, the bioactivation of carcinogens, and the detoxification of xenobiotics. Knowledge of the structural and mechanistic basis of substrate specificity and activity is crucial for understanding steroid and hormone metabolism, drug sensitivity, pharmacogenomics, and response to environmental toxins. We have determined the crystal structures of five hSULTs for which structural information was lacking, and screened nine of the 12 hSULTs for binding and activity toward a panel of potential substrates and inhibitors, revealing unique “chemical fingerprints” for each protein. The family-wide analysis of the screening and structural data provides a comprehensive, high-level view of the determinants of substrate binding, the mechanisms of inhibition by substrates and environmental toxins, and the functions of the orphan family members SULT1C3 and SULT4A1. Evidence is provided for structural “priming” of the enzyme active site by cofactor binding, which influences the spectrum of small molecules that can bind to each enzyme. The data help explain substrate promiscuity in this family and, at the same time, reveal new similarities between hSULT family members that were previously unrecognized by sequence or structure comparison alone.

  人体细胞质磺基转移酶（hSULTs）由12种II期酶组成，参与药物和激素代谢、致癌物质的生物活化以及异生物的解毒。了解底物特异性和活性的结构和机理基础对于理解类固醇和激素代谢、药物敏感性、药物基因组学以及对环境毒素的反应至关重要。我们确定了五种hSULTs的晶体结构，这些结构信息此前一直缺失，并对12种hSULTs中的9种进行了筛选，以确定其对一组潜在底物和抑制剂的结合和活性，揭示了每种蛋白质独特的“化学指纹”。通过筛选和结构数据的家族分析，我们全面、深入地了解了底物结合的决定因素、底物和环境毒素的抑制机理，以及孤儿家族成员SULT1C3和SULT4A1的功能。实验证据表明，辅因子结合对酶活性位点的结构“启动”有影响，从而影响可与每种酶结合的小分子谱。这些数据有助于解释该家族中底物的杂合性，同时揭示了hSULT家族成员之间新的相似性，而此前仅通过序列或结构比较无法识别这些相似性。
• Bacterial expression and characterization of a cDNA for human liver estrogen sulfotransferase
  作者：Charles N. Falany、Victor Krasnykh、Josie L. Falany

  DOI：10.1016/0960-0760(95)00015-r

  日期：1995.6

  A distinct human estrogen sulfotransferase (hEST-1) cDNA has been isolated from a human liver lambda Zap cDNA library using a PCR procedure. The enzymatically active protein has been expressed in two bacterial expression systems and the kinetic and immunologic properties of the enzyme have been characterized. The full-length cDNA for hEST-1 is 994 base pairs in length and encodes a 294 amino acid protein

  使用PCR程序已从人肝λZap cDNA文库中分离出独特的人雌激素磺基转移酶（hEST-1）cDNA。酶促活性蛋白已经在两个细菌表达系统中表达，并且已经表征了该酶的动力学和免疫学特性。hEST-1的全长cDNA长994个碱基对，编码294个氨基酸蛋白质，计算的分子量为35123 Da。在SDS-聚丙烯酰胺凝胶电泳过程中，纯化的hEST-1以35,000 Da的表观分子量迁移。用兔抗hEST-1抗体在大肠杆菌中表达的hEST-1的免疫印迹分析产生约35,000 Da的条带。抗-hEST-1抗体还检测到人类肝脏和空肠细胞质中的一条条带，该条带以与表达的hEST-1相同的分子量迁移。免疫印迹分析后，hEST-1与兔抗-hP-PST或兔抗-hDHEA-ST抗体也没有交叉反应。hEST-1在细菌中表达并纯化至同质。表达的hEST-1活性对雌激素硫酸盐的亲和力比结合其他雌激素的其他人类STs的亲和力大得多。hEST-1在浓度为20
• Crystal Structure of the Human Estrogen Sulfotransferase-PAPS Complex
  作者：Lars C. Pedersen、Evgeniy Petrotchenko、Sergei Shevtsov、Masahiko Negishi

  DOI：10.1074/jbc.m111651200

  日期：2002.5

  Estrogen sulfotransferase (EST) transfers the sulfate group from T-phosphoadenosine 5'-phosphosulfate (PAPS) to estrogenic steroids. Here we report the crystal structure of human EST (hEST) in the context of the V269E mutant-PAPS complex, which is the first structure containing the active sulfate donor for any sulfotransferase. Superimposing this structure with the crystal structure of hEST in complex with the donor product 3'-phosphoadenosine 5'-phosphate (PAP) and the acceptor substrate 17beta-estradiol, the ternary structure with the PAPS and estradiol molecule, is modeled. These structures have now provided a more complete view of the S(N)2-like in-line displacement reaction catalyzed by sulfotransferases. In the PAPS-bound structure, the side chain nitrogen of the catalytic Lys(47) interacts with the side chain hydroxyl of Ser(137) and not with the bridging oxygen between the 5'-phosphate and sulfate groups of the PAPS molecule as is seen in the PAP-bound structures. This conformational change of the side chain nitrogen indicates that the interaction of Lys(47) with Ser(137) may regulate PAPS hydrolysis in the absences of an acceptor substrate. Supporting the structural data, the mutations of Ser(137) to cysteine and alanine decrease gradually k(cat) for PAPS hydrolysis and transfer activity. Thus, Ser(137) appears to play an important role in regulating the side chain interaction of Lys(47) with the bridging oxygen between the 5'-phosphate and the sulfate of PAPS.
• The Sulfuryl Transfer Mechanism
  作者：Yoshimitsu Kakuta、Evgeny V. Petrotchenko、Lars C. Pedersen、Masahiko Negishi

  DOI：10.1074/jbc.273.42.27325

  日期：1998.10

  Estrogen sulfotransferase (EST) catalyzes transfer of the 5'-sulfuryl group of adenosine 3'-phosphate 5'-phosphosulfate (PAPS) to the 3 alpha-phenol group of estrogenic steroids such as estradiol (E-2), The recent crystal structure of EST adenosine 3',5'-diphosphate (PAP)- E-2 complex has revealed that residues Lys(48), Thr(45) Thr(51), Thr(52), Lys(106), His(108), and Try(240) are in position to play a catalytic role in the sulfuryl transfer reaction of EST (Kakuta Y., Pedersen, L. G., Carter, C. W., Negishi, M., and Pedersen, L. C. (1997) Nat. Struct. BioL. 4, 904-908). Mutation of Lys(48), Lys(106), or His(108) nearly abolishes EST activity, indicating that they play a critical role in catalysis, A present 2.2-A resolution structure of EST-PAP-vanadate complex indicates that the vanadate molecule adopts a trigonal bipyramidal geometry with its equatorial oxygens coordinated to these three residues. The apical positions of the vanadate molecule are occupied by a terminal oxygen of the 5'-phosphate of PAP (2.1 ) and a possible water molecule (2.3 Angstrom), This water molecule superimposes well to the 3 alpha-phenol group of E-2 in the crystal structure of the EST . PAP . E-2 complex. These structures are characteristic of the transition state for an in-line sulfuryl transfer reaction from PAPS to E-2. Moreover, residues Lys(48), Lys(106), His(108) are found to be coordinated with the vanadate molecule at the transition state of EST.