thioglycolic acid | 856604-62-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: thioglycolic acid
• 英文别名: 1-Hydroxy-3-sulfanylpropan-2-one
• CAS: 856604-62-1
• 化学式: C₃H₆O₂S
• 分子量: 106.145
• InChiKey: PBFVUKHZUJVMLL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  6
• 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：
  38.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  thioglycolic acid 在 sodium hydroxide 、 protein tyrosine phosphatase 1B 作用下， 以 重水 为溶剂， 生成
  参考文献：
  名称：

  Thiol-Dependent Recovery of Catalytic Activity from Oxidized Protein Tyrosine Phosphatases

  摘要：

  Protein tyrosine phosphatases (PTPs) play an important role in the regulation of mammalian signal transduction. During some cell signaling processes, the generation of endogenous hydrogen peroxide inactivates selected PTPs via oxidation of the enzyme's catalytic cysteine thiolate group. Importantly, low-molecular weight and protein thiols in the cell have the potential to regenerate the catalytically active PTPs. Here we examined the recovery of catalytic activity from two oxidatively inactivated PTPs (PTP1B and SHP-2) by various low-molecular weight thiols and the enzyme thioredoxin. All monothiols examined regenerated the catalytic activity of oxidized PTP1B, with apparent rate constants that varied by a factor of approximately 8. In general, molecules bearing thiol groups were particularly effective. The biological thiol glutathione repaired oxidized PTP1B with an apparent second-order rate constant of 0.023 +/- 0.004 M-1 s(-1), while the dithiol dithiothreitol (DTT) displayed an apparent second-order rate constant of 0.325 +/- 0.007 M-1 s(-1). The enzyme thioredoxin regenerated the catalytic activity of oxidized PTP1B at a substantially faster rate than DTT. Thioredoxin (2 mu M) converted oxidized PTP1B to the active form with an observed rate constant of 1.4 x 10(-3) s(-1). The rates at which these agents regenerated oxidized PTP1B followed the order Trx > DTT > GSHand comparable values observed at 2 mu M Trx, 4 mM DTT, and 60 mM GSH. Various disulfides that are byproducts of the reactivation process did not inactivate native PTP1B at concentrations of 1-20 mM. The common biochemical reducing agent tris(2-carboxyethyl)phosphine regenerates enzymatic activity from oxidized PTP1B somewhat faster than the thiol-based reagents, with a rate constant of 1.5 +/- 0.5 M-1 s(-1). We observed profound kinetic differences between the thiol-dependent regeneration of activity from oxidized PTP1B and SHP-2, highlighting the potential for structural differences in various oxidized PTPs to play a significant role in the rates at which low-molecular weight thiols and thiol-containing enzymes such as thioredoxin and glutaredoxin return catalytic activity to these enzymes during cell signaling events.

  DOI：

  10.1021/bi400451m

文献信息

• Thiol-Dependent Recovery of Catalytic Activity from Oxidized Protein Tyrosine Phosphatases
  作者：Zachary D. Parsons、Kent S. Gates

  DOI：10.1021/bi400451m

  日期：2013.9.17

  Protein tyrosine phosphatases (PTPs) play an important role in the regulation of mammalian signal transduction. During some cell signaling processes, the generation of endogenous hydrogen peroxide inactivates selected PTPs via oxidation of the enzyme's catalytic cysteine thiolate group. Importantly, low-molecular weight and protein thiols in the cell have the potential to regenerate the catalytically active PTPs. Here we examined the recovery of catalytic activity from two oxidatively inactivated PTPs (PTP1B and SHP-2) by various low-molecular weight thiols and the enzyme thioredoxin. All monothiols examined regenerated the catalytic activity of oxidized PTP1B, with apparent rate constants that varied by a factor of approximately 8. In general, molecules bearing thiol groups were particularly effective. The biological thiol glutathione repaired oxidized PTP1B with an apparent second-order rate constant of 0.023 +/- 0.004 M-1 s(-1), while the dithiol dithiothreitol (DTT) displayed an apparent second-order rate constant of 0.325 +/- 0.007 M-1 s(-1). The enzyme thioredoxin regenerated the catalytic activity of oxidized PTP1B at a substantially faster rate than DTT. Thioredoxin (2 mu M) converted oxidized PTP1B to the active form with an observed rate constant of 1.4 x 10(-3) s(-1). The rates at which these agents regenerated oxidized PTP1B followed the order Trx > DTT > GSHand comparable values observed at 2 mu M Trx, 4 mM DTT, and 60 mM GSH. Various disulfides that are byproducts of the reactivation process did not inactivate native PTP1B at concentrations of 1-20 mM. The common biochemical reducing agent tris(2-carboxyethyl)phosphine regenerates enzymatic activity from oxidized PTP1B somewhat faster than the thiol-based reagents, with a rate constant of 1.5 +/- 0.5 M-1 s(-1). We observed profound kinetic differences between the thiol-dependent regeneration of activity from oxidized PTP1B and SHP-2, highlighting the potential for structural differences in various oxidized PTPs to play a significant role in the rates at which low-molecular weight thiols and thiol-containing enzymes such as thioredoxin and glutaredoxin return catalytic activity to these enzymes during cell signaling events.