CysSA | 66626-24-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: CysSA
• 英文别名: (L-cysteinyl)adenylate；[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl [(2R)-2-azaniumyl-3-sulfanylpropanoyl] phosphate
• CAS: 66626-24-2
• 化学式: C₁₃H₁₉N₆O₈PS
• 分子量: 450.369
• InChiKey: CHQCHJWWSCSGOJ-MACXSXHHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.8
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  219
• 氢给体数：
  6
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  O-(pantetheine-4ʼ-phosphoryl)-L-serine residue 、 CysSA 生成 adenosine 5'-monophosphate 、 氢(+1)阳离子 、 O-[S-(L-cysteinyl)pantetheine-4'-phosphoryl]-L-serine residue
  参考文献：
  名称：

  Assembly of the Pseudomonas aeruginosa Nonribosomal Peptide Siderophore Pyochelin:  In Vitro Reconstitution of Aryl-4,2-bisthiazoline Synthetase Activity from PchD, PchE, and PchF

  摘要：

  Three Pseudomonas aeruginosa proteins involved in biogenesis of the nonribosomal peptide siderophore pyochelin, PchD, PchE, and PchF, have been expressed in and purified from Escherichia coli and are found to produce the tricyclic acid hydroxyphenyl-thiazolyl-thiazolinyl-carboxylic acid (HPTT-COOH), an advanced intermediate containing the aryl-4,2-bis-heterocyclic skeleton of the bithiazoline class of siderophores. The three proteins contain three adenylation domains, one specific for salicylate activation and two specific for cysteine activation, and three carrier protein domains (two in PchE and one in PchF) that undergo posttranslational priming With phosphopantetheine to enable covalent-tethering of salicyl and cysteinyl moieties as acyl-S-enzyme intermediates,Two cyclization domains (Cyl in PchE and Cy2 in PchF) create the two amide linkages in the elongating chains and the cyclodehydrations of acylcysteine moieties into thiazolinyl rings. The ninth domain, the most downstream domain in PchF, is the chain-terminating, acyl-S-enzyme thioester hydrolase that releases the HPTT-S-enzyme intermediate to the observed tandem bis-heterocyclic acid product. A PchF-thioesterase domain active site double mutant fails to turn over, but a monocyclic hydroxyphenyl-thiazolinyl-cysteine (HPT-Cys) product continues to be released from PchE, allowing assignment of the cascade of acyl-S-enzyme intermediates involved in initiation, elongation, and termination steps.

  DOI：

  10.1021/bi991787c
• 作为产物：
  描述：

  L-半胱氨酸 、 5’-三磷酸腺苷 在 maize organellar seryl-tRNA synthetase 、 potassium chloride 、 manganese(ll) chloride 作用下， 以 aq. phosphate buffer 为溶剂， 生成 CysSA
  参考文献：
  名称：

  玉米丝氨酰-tRNA合成酶的底物识别和保真度。

  摘要：

  氨酰基-tRNA合成酶（aaRSs）催化氨基酸与其同源tRNA的结合，从而建立遗传密码。为了获得在翻译中观察到的高度准确性，这些酶必须对其同源氨基酸和tRNA表现出严格的底物特异性。我们研究了玉米胞浆丝氨酸-tRNA合成酶（SerRS）对tRNA（Ser）识别的要求。该酶有效识别细菌和真核tRNA（Ser），表明它可以适应各种类型的tRNA（Ser）结构。鉴别基G73对于胞浆SerRS的识别至关重要。尽管胞质SerRS有效识别细菌tRNA（Ser），但它仅局限在胞质溶胶中。比较了玉米胞浆和双重靶向细胞器SerRS在氨基酸识别方面的保真度。与胞质对应物相比，细胞器SerRS对测试的非同源底物表现出更高的区分度。两种酶均显示出转移前的编辑活性，这表明它们具有较高的整体准确性。玉米酶在转移前编辑反应中各种反应途径的贡献是不同的，并且取决于非同源底物。玉米细胞器SerRS的保真机制，高判别力和校对

  DOI：

  10.1016/j.abb.2012.11.014

文献信息

• Adenylation and <i>S</i>-Methylation of Cysteine by the Bifunctional Enzyme TioN in Thiocoraline Biosynthesis
  作者：Ahmad H. Al-Mestarihi、Germán Villamizar、Javier Fernández、Olga E. Zolova、Felipe Lombó、Sylvie Garneau-Tsodikova

  DOI：10.1021/ja510489j

  日期：2014.12.10

  The antitumor agent thiocoraline is a nonribosomally biosynthesized bisintercalator natural product, which contains in its peptidic backbone two S-methylated l-cysteine residues. S-Methylation occurs very rarely in nature, and is observed extremely rarely in nonribosomal peptide scaffolds. We have proposed that during thiocoraline biosynthesis, TioN, a stand-alone adenylation domain interrupted by the S-adenosyl-l-methionine binding region of a methyltransferase enzyme, is capable of performing two functions: the adenylation and S-methylation of l-cysteine. Herein, by preparation of knockouts of TioN and its MbtH-like protein partner TioT, we confirmed their role in thiocoraline biosynthesis. We also co-expressed recombinant TioN and TioT and biochemically investigated three potential pathways involving activation, methylation, and loading of l-cysteine onto the TioN partner thiolation domain, TioS(T4). The valuable insights gained into the pathway(s) followed for the production of S-Me-l-Cys-S-TioS(T4) will serve as a guide for the development of novel engineered interrupted adenylation enzymes for combinatorial biosynthesis.
• Substrate recognition and fidelity of maize seryl-tRNA synthetases
  作者：Jasmina Rokov-Plavec、Sonja Lesjak、Ita Gruic-Sovulj、Marko Mocibob、Morana Dulic、Ivana Weygand-Durasevic

  DOI：10.1016/j.abb.2012.11.014

  日期：2013.1

  Aminoacyl-tRNA synthetases (aaRSs) catalyze the attachment of amino acids to their cognate tRNAs to establish the genetic code. To obtain the high degree of accuracy that is observed in translation, these enzymes must exhibit strict substrate specificity for their cognate amino acids and tRNAs. We studied the requirements for tRNA(Ser) recognition by maize cytosolic seryl-tRNA synthetase (SerRS). The

  氨酰基-tRNA合成酶（aaRSs）催化氨基酸与其同源tRNA的结合，从而建立遗传密码。为了获得在翻译中观察到的高度准确性，这些酶必须对其同源氨基酸和tRNA表现出严格的底物特异性。我们研究了玉米胞浆丝氨酸-tRNA合成酶（SerRS）对tRNA（Ser）识别的要求。该酶有效识别细菌和真核tRNA（Ser），表明它可以适应各种类型的tRNA（Ser）结构。鉴别基G73对于胞浆SerRS的识别至关重要。尽管胞质SerRS有效识别细菌tRNA（Ser），但它仅局限在胞质溶胶中。比较了玉米胞浆和双重靶向细胞器SerRS在氨基酸识别方面的保真度。与胞质对应物相比，细胞器SerRS对测试的非同源底物表现出更高的区分度。两种酶均显示出转移前的编辑活性，这表明它们具有较高的整体准确性。玉米酶在转移前编辑反应中各种反应途径的贡献是不同的，并且取决于非同源底物。玉米细胞器SerRS的保真机制，高判别力和校对
• Assembly of the <i>Pseudomonas aeruginosa</i> Nonribosomal Peptide Siderophore Pyochelin:  In Vitro Reconstitution of Aryl-4,2-bisthiazoline Synthetase Activity from PchD, PchE, and PchF
  作者：Luis E. N. Quadri、Thomas A. Keating、Hiten M. Patel、Christopher T. Walsh

  DOI：10.1021/bi991787c

  日期：1999.11.1

  Three Pseudomonas aeruginosa proteins involved in biogenesis of the nonribosomal peptide siderophore pyochelin, PchD, PchE, and PchF, have been expressed in and purified from Escherichia coli and are found to produce the tricyclic acid hydroxyphenyl-thiazolyl-thiazolinyl-carboxylic acid (HPTT-COOH), an advanced intermediate containing the aryl-4,2-bis-heterocyclic skeleton of the bithiazoline class of siderophores. The three proteins contain three adenylation domains, one specific for salicylate activation and two specific for cysteine activation, and three carrier protein domains (two in PchE and one in PchF) that undergo posttranslational priming With phosphopantetheine to enable covalent-tethering of salicyl and cysteinyl moieties as acyl-S-enzyme intermediates,Two cyclization domains (Cyl in PchE and Cy2 in PchF) create the two amide linkages in the elongating chains and the cyclodehydrations of acylcysteine moieties into thiazolinyl rings. The ninth domain, the most downstream domain in PchF, is the chain-terminating, acyl-S-enzyme thioester hydrolase that releases the HPTT-S-enzyme intermediate to the observed tandem bis-heterocyclic acid product. A PchF-thioesterase domain active site double mutant fails to turn over, but a monocyclic hydroxyphenyl-thiazolinyl-cysteine (HPT-Cys) product continues to be released from PchE, allowing assignment of the cascade of acyl-S-enzyme intermediates involved in initiation, elongation, and termination steps.