N⁸-Mono-glutathionylspermidine

• 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: N⁸-Mono-glutathionylspermidine
• 英文别名: glutathionylspermidine；(2S)-2-amino-5-[[(2R)-1-[[2-[4-(3-aminopropylamino)butylamino]-2-oxoethyl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-5-oxopentanoic acid
• 化学式: C₁₇H₃₄N₆O₅S
• 分子量: 434.56
• InChiKey: OAYJMZFEKFGKBY-STQMWFEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5
• 重原子数：
  29
• 可旋转键数：
  17
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  190
• 氢给体数：
  8
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N⁸-Mono-glutathionylspermidine 在 Trypanosoma brucei trypanothione synthetase 作用下， 以 aq. buffer 为溶剂， 生成 谷胱甘肽
  参考文献：
  名称：

  Dissecting the Catalytic Mechanism of Trypanosoma brucei Trypanothione Synthetase by Kinetic Analysis and Computational Modeling

  摘要：

  In pathogenic trypanosomes, trypanothione synthetase (TryS) catalyzes the synthesis of both glutathionylspermidine (Gsp) and trypanothione (bis(glutathionyl) spermidine (T(SH)(2))). Here we present a thorough kinetic analysis of Trypanosoma brucei TryS in a newly developed phosphate buffer system at pH 7.0 and 37 degrees C, mimicking the physiological environment of the enzyme in the cytosol of bloodstream parasites. Under these conditions, TryS displays K-m values for GSH, ATP, spermidine, and Gsp of 34, 18, 687, and 32 mu M, respectively, as well as K-i values for GSH and T(SH) 2 of 1 mM and 360 mu M, respectively. As Gsp hydrolysis has a K-m value of 5.6 mM, the in vivo amidase activity is probably negligible. To obtain deeper insight in the molecular mechanism of TryS, we have formulated alternative kinetic models, with elementary reaction steps represented by linear kinetic equations. The model parameters were fitted to the extensive matrix of steady-state data obtained for different substrate/product combinations under the in vivo-like conditions. The best model describes the full kinetic profile and is able to predict time course data that were not used for fitting. This system's biology approach to enzyme kinetics led us to conclude that (i) TryS follows a ter-reactant mechanism, (ii) the intermediate Gsp dissociates from the enzyme between the two catalytic steps, and (iii) T(SH)(2) inhibits the enzyme by remaining bound at its product site and, as does the inhibitory GSH, by binding to the activated enzyme complex. The newly detected concerted substrate and product inhibition suggests that TryS activity is tightly regulated.

  DOI：

  10.1074/jbc.m113.483289
• 作为产物：
  描述：

  5-(2,5-二氧代-1-吡咯烷基)1-(2-甲基-2-丙基)N-{[(2-甲基-2-丙基)氧基]羰基}-L-谷氨酸 在 吡啶 、 丙二酸 、 三氟乙酸 、 1,4-二巯基-2,3-丁二醇 、 氯甲酸异丁酯 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.75h， 生成 N⁸-Mono-glutathionylspermidine
  参考文献：
  名称：

  锥虫代谢产物锥虫硫醚，N 1-单-和N 8-单-谷胱甘肽亚精胺的合成

  摘要：

  锥虫的代谢产物锥虫[ N 1，N 8-双（谷胱甘肽）亚精胺]及其生物合成代谢物，N 1-和N 8-单-谷胱甘肽亚精胺异构体是通过温和的途径合成的，该方法涉及偶联甘氨酰基-亚精胺衍生物功能保护的γ-谷氨酰半胱氨酸二肽。

  DOI：

  10.1039/c39860000593

文献信息

• Dissecting the Catalytic Mechanism of Trypanosoma brucei Trypanothione Synthetase by Kinetic Analysis and Computational Modeling
  作者：Alejandro E. Leroux、Jurgen R. Haanstra、Barbara M. Bakker、R. Luise Krauth-Siegel

  DOI：10.1074/jbc.m113.483289

  日期：2013.8

  In pathogenic trypanosomes, trypanothione synthetase (TryS) catalyzes the synthesis of both glutathionylspermidine (Gsp) and trypanothione (bis(glutathionyl) spermidine (T(SH)(2))). Here we present a thorough kinetic analysis of Trypanosoma brucei TryS in a newly developed phosphate buffer system at pH 7.0 and 37 degrees C, mimicking the physiological environment of the enzyme in the cytosol of bloodstream parasites. Under these conditions, TryS displays K-m values for GSH, ATP, spermidine, and Gsp of 34, 18, 687, and 32 mu M, respectively, as well as K-i values for GSH and T(SH) 2 of 1 mM and 360 mu M, respectively. As Gsp hydrolysis has a K-m value of 5.6 mM, the in vivo amidase activity is probably negligible. To obtain deeper insight in the molecular mechanism of TryS, we have formulated alternative kinetic models, with elementary reaction steps represented by linear kinetic equations. The model parameters were fitted to the extensive matrix of steady-state data obtained for different substrate/product combinations under the in vivo-like conditions. The best model describes the full kinetic profile and is able to predict time course data that were not used for fitting. This system's biology approach to enzyme kinetics led us to conclude that (i) TryS follows a ter-reactant mechanism, (ii) the intermediate Gsp dissociates from the enzyme between the two catalytic steps, and (iii) T(SH)(2) inhibits the enzyme by remaining bound at its product site and, as does the inhibitory GSH, by binding to the activated enzyme complex. The newly detected concerted substrate and product inhibition suggests that TryS activity is tightly regulated.
• Synthesis of the trypanosomatid metabolites trypanothione, and N 1-mono- and N 8-mono-glutathionylspermidine
  作者：Graeme B. Henderson、Peter Ulrich、Alan H. Fairlamb、Anthony Cerami

  DOI：10.1039/c39860000593

  日期：——

  The trypanosomatid metabolite trypanothione [N1,N8-bis(glutathionyl)spermidine] and its biosynthetic co-metabolites the isomeric N1- and N8-mono-glutathionylspermidines have been synthesised by a mild route which involves coupling of glycinyl-spermidine derivatives to a functionally protected γ-glutamylcysteine dipeptide.

  锥虫的代谢产物锥虫[ N 1，N 8-双（谷胱甘肽）亚精胺]及其生物合成代谢物，N 1-和N 8-单-谷胱甘肽亚精胺异构体是通过温和的途径合成的，该方法涉及偶联甘氨酰基-亚精胺衍生物功能保护的γ-谷氨酰半胱氨酸二肽。