3-羟基-5-甲基-L-酪氨酸

• 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
• 中文名称: 3-羟基-5-甲基-L-酪氨酸
• 英文名称: 3-(3,4-dihydroxy-5-methylphenyl)-L-alanine
• 英文别名: 3-hydroxy-5-methyl-L-tyrosine；3-OH-5-Me-L-Tyr；3-OH-5-Me-Tyr；(2S)-2-ammonio-3-(3,4-dihydroxy-5-methylphenyl)propanoate；(2S)-2-azaniumyl-3-(3,4-dihydroxy-5-methylphenyl)propanoate
• 化学式: C₁₀H₁₃NO₄
• 分子量: 211.218
• InChiKey: BIPUEBQLNUMSEB-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  104
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-羟基-5-甲基-L-酪氨酸 、 S-腺苷蛋氨酸 生成 3-(3-hydroxy-4-methoxy-5-methylphenyl)-L-alanine 、 氢(+1)阳离子 、 S-(5'-腺苷)-L-高半胱氨酸
  参考文献：
  名称：

  Characterization of SfmD as a Heme Peroxidase That Catalyzes the Regioselective Hydroxylation of 3-Methyltyrosine to 3-Hydroxy-5-methyltyrosine in Saframycin A Biosynthesis

  摘要：

  Saframycin A (SFM-A) is a potent antitumor antibiotic that belongs to the tetrahydroisoquinoline family. Biosynthetic studies have revealed that its unique pentacyclic core structure is derived from alanine, glycine, and non-proteinogenic amino acid 3-hydroxy-5-methyl-O-methyltyrosine (3-OH-5-Me-OMe-Tyr). SfmD, a hypothetical protein in the biosynthetic pathway of SFM-A, was hypothesized to be responsible for the generation of the 3-hydroxy group of 3-OH-5-Me-OMe-Tyr based on previously heterologous expression results. We now report the in vitro characterization of SfmD as a novel hemecontaining peroxidase that catalyzes the hydroxylation of 3-methyltyrosine to 3-hydroxy-5-methyltyrosine using hydrogen peroxide as the oxidant. In addition, we elucidated the biosynthetic pathway of 3-OH-5-Me-OMe-Tyr by kinetic studies of SfmD in combination with biochemical assays of SfmM2, a methyltransferase within the same pathway. Furthermore, SacD, a counterpart of SfmD involved in safracin B biosynthesis, was also characterized as a heme-containing peroxidase, suggesting that SfmD-like heme-containing peroxidases may be commonly involved in the biosynthesis of SFM-A and its analogs. Finally, we found that the conserved motif HXXXC is crucial for heme binding using comparative UV-Vis and Magnetic Circular Dichroism (MCD) spectra studies of SfmD wild-type and mutants. Together, these findings expand the category of heme-containing peroxidases and set the stage for further mechanistic studies. In addition, this study has critical implications for delineating the biosynthetic pathway of other related tetrahydroisoquinoline family members.

  DOI：

  10.1074/jbc.m111.306316
• 作为产物：
  描述：

  3-甲基-L-酪氨酸 在 氧气 、 heme peroxidase SfmD, full-length, tag-free 、 维生素 C 作用下， 生成 3-羟基-5-甲基-L-酪氨酸
  参考文献：
  名称：

  通过从头晶体结构和光谱研究揭示了 SfmD 中具有单硫醚键和双组氨酸配体组的新型催化血红素辅助因子

  摘要：

  SfmD 是 Saframycin A 生物合成途径中的一种血红素依赖性酶。在这里，我们展示了 SfmD 的 1.78 Å 分辨率从头晶体结构，它揭示了一种新型血红素辅助因子，该辅助因子以不寻常的H x n H xxx C基序附着在蛋白质上（ n ～38）。这种血红素辅因子在两个方面是独特的。它在与Cys317的半胱氨酸-乙烯基连接中包含单个硫醚键，并且铁血红素具有两个轴向蛋白配体，即His274和His313​​。我们证明了 SfmD 血红素具有催化活性，可以利用双氧和抗坏血酸将单氧插入 3-甲基-L-酪氨酸中。使用抗坏血酸衍生物的催化测定揭示了抗坏血酸的官能团对于其作为共底物的功能至关重要。通过 Cys317 突变消除硫醚键会产生催化失活的 SfmD 变体。 EPR 和光学数据显示，血红素中心发生显着构象变化，响应底物 3-甲基-L-酪氨酸结合或通过还原剂（例如共底物抗坏血酸）进行化学

  DOI：

  10.1039/d0sc06369j

文献信息

• Monomethylvaline Compounds Having Phenylalanine Side-Chain Replacements at the C-Terminus
  申请人：Doronina Svetlana O.

  公开号：US20090018086A1

  公开（公告）日：2009-01-15

  Auristatin peptide analogs of MeVal-Val-Dil-Dap-Phe (MMAF) are provided having C-terminal phenylalanine residue side chain replacements or modifications which are provided alone or attached to ligands through various linkers. The related conjugates can target specific cell types to provide therapeutic benefit.

  提供了MeVal-Val-Dil-Dap-Phe（MMAF）的Auristatin肽类类似物，其中包括C-末端苯丙氨酸残基侧链替换或修饰，这些类似物可以单独提供或通过各种连接剂连接到配体上。相关的结合物可以针对特定细胞类型，提供治疗效果。
• MONOMETHYLVALINE COMPOUNDS HAVING PHENYLALANINE SIDE-CHAIN MODIFICATIONS AT THE C-TERMINUS
  申请人：Seattle Genetics, Inc.

  公开号：US20130123465A1

  公开（公告）日：2013-05-16

  Auristatin peptide analogs of MeVal-Val-Dil-Dap-Phe (MMAF) are provided having C-terminal phenylalanine residue side chain replacements or modifications which are provided alone or attached to ligands through various linkers. The related conjugates can target specific cell types to provide therapeutic benefit.

  提供了MeVal-Val-Dil-Dap-Phe（MMAF）的Auristatin肽类类似物，其具有C-末端苯丙氨酸残基侧链替换或修饰，可单独提供或通过各种连接剂连接到配体上。相关的结合物可以定向特定的细胞类型，以提供治疗效益。
• Monomethylvaline compounds having phenylalanine side-chain modification at the C-terminus
  申请人：Seattle Genetics, Inc.

  公开号：US10000555B2

  公开（公告）日：2018-06-19

  Auristatin peptide analogs of MeVal-Val-Dil-Dap-Phe (MMAF) are provided having C-terminal phenylalanine residue side chain replacements or modifications which are provided alone or attached to ligands through various linkers. The related conjugates can target specific cell types to provide therapeutic benefit.

  提供的 MeVal-Val-Dil-Dap-Phe (MMAF) Auristatin 肽类似物具有 C 端苯丙氨酸残基侧链替换或修饰，可单独提供或通过各种连接体连接到配体上。相关共轭物可靶向特定细胞类型，提供治疗效果。
• Synthesis of tyrosine derivatives for saframycin MX1 biosynthetic studies
  作者：Eric W. Schmidt、James T. Nelson、John P. Fillmore

  DOI：10.1016/j.tetlet.2004.03.112

  日期：2004.5

  Saframycin MX1 and structural relatives are natural anticancer agents isolated from bacteria and marine invertebrates. For biosynthetic studies and to make a library of modified natural products, a series of tyrosine derivatives were synthesized in a concise manner. (C) 2004 Elsevier Ltd. All rights reserved.
• US8343928B2
  申请人：——

  公开号：US8343928B2

  公开（公告）日：2013-01-01