3′-hydroxy-T-2 | 84474-35-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 3′-hydroxy-T-2
• 英文别名: 3'-hydroxy-T-2-toxin；TC-1 toxin；3'-hydroxy-T-2 toxin；3'-OH-T-2 toxin；3'-OH-T2；3'-hydroxy T-2 toxin；[(1S,2R,4S,7R,9R,10R,11S,12S)-11-acetyloxy-2-(acetyloxymethyl)-10-hydroxy-1,5-dimethylspiro[8-oxatricyclo[7.2.1.02,7]dodec-5-ene-12,2'-oxirane]-4-yl] 3-hydroxy-3-methylbutanoate
• CAS: 84474-35-1
• 化学式: C₂₄H₃₄O₁₀
• 分子量: 482.528
• InChiKey: MLDQZNYFEGLVAS-GGTUAJKXSA-N

物化性质

• 沸点：
  599.5±50.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  141
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  T-2 toxin 在 magnesium dicarbide 、 谷胱甘肽 、 cytochrome b5 、 recombinant pig CYP₃A₂₂ (Leu₃₆Arg, Gly₃₇Glu, Ile₃₈Lys and Pro₃₉Arg mutant with additional Glu-Arg at the N-terminus) 、 1,2-二油酰基-sn-甘油-3-磷酸胆碱 、 3-[(3-cholamidopropyl)dimethylammonio]propanesulfonate 、 还原型辅酶II(NADPH)四钠盐 、 NADPH---hemoprotein reductase 作用下， 反应 3.0h， 生成 3′-hydroxy-T-2
  参考文献：
  名称：

  The catalytic activity of cytochrome P450 3A22 is critical for the metabolism of T-2 toxin in porcine reservoirs

  摘要：

  Contamination of food by T 2 toxin a trichothecene mycotoxin poses a serious threat to human health We report the identification of cytochrome P450 3A22 (CYP3A22) responsible for 3' hydroxylation of T-2 and HT-2 in pigs The present study shows that T-2 toxin significantly induces CYP3A22 expression in primary piglet hepatocytes Moreover recombinant pig CYP3A22 converted T-2 toxin into TC-1 (3'-OH T-2 toxin) and HT 2 toxin into TC-3 (3'-OH HT-2 toxin) in vitro These results suggest that pig CYP3A22 primarily eliminates T-2 and HT-2 toxins by 3'-hydroxylation of isovaleryl groups Therefore CYP3A22 is critical for xenobiotic metabolism and endogenous biochemical biotransformation of trichothecene mycotoxin in porcine reservoirs (C) 2010 Elsevier B V All rights reserved

  DOI：

  10.1016/j.catcom.2010.08.003

文献信息

• Structure-Function Analysis of Porcine Cytochrome P450 3A29 in the Hydroxylation of T-2 Toxin as Revealed by Docking and Mutagenesis Studies
  作者：Guyue Cheng、Changcun Liu、Xu Wang、Hongmin Ma、Yuanhu Pan、Lingli Huang、Haihong Hao、Menghong Dai、Zonghui Yuan

  DOI：10.1371/journal.pone.0106769

  日期：——

  T-2 toxin, one of the type A trichothecenes, presents a potential hazard to human and animal health. Our previous work demonstrated that porcine cytochrome P450 3A29 (CYP3A29) played an important role in the hydroxylation of T-2 toxin. To identify amino acids involved in this metabolic process, T-2 toxin was docked into a homology model of CYP3A29 based on a crystal structure of CYP3A4 using AutoDock 4.0. Nine residues of CYP3A29, Arg105, Arg106, Phe108, Ser119, Lys212, Phe213, Phe215, Arg372 and Glu374, which were found within 5 Å around T-2 toxin were subjected to site-directed mutagenesis. In the oxidation of nifedipine, the CLint value of R106A was increased by nearly two-folds compared with the wild-type CYP3A29, while the substrate affinities and CLint values of S119A and K212A were significantly reduced. In the hydroxylation of T-2 toxin, the generation of 3′-OH-T-2 by R105A, S119A and K212A was significantly less than that by the wild-type, whereas R106A slightly increased the generation of 3′-OH-T-2. These results were further confirmed by isothermal titration calorimetry analysis, suggesting that these four residues are important in the hydroxylation of T-2 toxin and Arg105 may be a specific recognition site for the toxin. Our study suggests a possible structure-function relationship of CYP3A29 in the hydroxylation of T-2 toxin, providing with new insights into the mechanism of CYP3A enzymes in the biotransformation of T-2 toxin.

  T-2 毒素是 A 型单端孢霉烯的一种，对人类和动物健康具有潜在危害。我们之前的研究表明，猪细胞色素 P450 3A29 (CYP3A29) 在 T-2 毒素的羟化过程中发挥了重要作用。为了确定参与这一代谢过程的氨基酸，我们使用 AutoDock 4.0 根据 CYP3A4 的晶体结构将 T-2 毒素与 CYP3A29 的同源模型对接。对 T-2 毒素周围 5 Å 范围内的 CYP3A29 的 9 个残基 Arg105、Arg106、Phe108、Ser119、Lys212、Phe213、Phe215、Arg372 和 Glu374 进行了定点突变。在硝苯地平的氧化过程中，与野生型 CYP3A29 相比，R106A 的 CLint 值增加了近两倍，而 S119A 和 K212A 的底物亲和力和 CLint 值则显著降低。在 T-2 毒素的羟化过程中，R105A、S119A 和 K212A 产生的 3′-OH-T-2 明显少于野生型，而 R106A 则略微增加了 3′-OH-T-2 的产生。等温滴定量热分析进一步证实了这些结果，表明这四个残基在 T-2 毒素的羟基化过程中非常重要，Arg105 可能是毒素的特异性识别位点。我们的研究提示了 CYP3A29 在 T-2 毒素羟化过程中可能存在的结构-功能关系，为了解 CYP3A 酶在 T-2 毒素生物转化过程中的作用机制提供了新的视角。
• The catalytic activity of cytochrome P450 3A22 is critical for the metabolism of T-2 toxin in porcine reservoirs
  作者：Xiaohu Ge、Junping Wang、Jing Liu、Jun Jiang、Huina Lin、Jun Wu、Man Ouyang、Xianqing Tang、Ming Zheng、Ming Liao、Yiqun Deng

  DOI：10.1016/j.catcom.2010.08.003

  日期：2010.11

  Contamination of food by T 2 toxin a trichothecene mycotoxin poses a serious threat to human health We report the identification of cytochrome P450 3A22 (CYP3A22) responsible for 3' hydroxylation of T-2 and HT-2 in pigs The present study shows that T-2 toxin significantly induces CYP3A22 expression in primary piglet hepatocytes Moreover recombinant pig CYP3A22 converted T-2 toxin into TC-1 (3'-OH T-2 toxin) and HT 2 toxin into TC-3 (3'-OH HT-2 toxin) in vitro These results suggest that pig CYP3A22 primarily eliminates T-2 and HT-2 toxins by 3'-hydroxylation of isovaleryl groups Therefore CYP3A22 is critical for xenobiotic metabolism and endogenous biochemical biotransformation of trichothecene mycotoxin in porcine reservoirs (C) 2010 Elsevier B V All rights reserved