coenzyme A | 31416-98-5

• 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: coenzyme A
• 英文别名: CoA-SH；CoA；[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(3S)-3-hydroxy-2,2-dimethyl-4-oxo-4-[[3-oxo-3-(2-sulfanylethylamino)propyl]amino]butyl] hydrogen phosphate
• CAS: 31416-98-5
• 化学式: C₂₁H₃₆N₇O₁₆P₃S
• 分子量: 767.541
• InChiKey: RGJOEKWQDUBAIZ-HDCXRZRFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.8
• 重原子数：
  48
• 可旋转键数：
  18
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  348
• 氢给体数：
  10
• 氢受体数：
  21

反应信息

• 作为反应物：
  描述：

  惕格酸 、 coenzyme A 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 3.5h， 生成 甲基巴豆酰-辅酶 A
  参考文献：
  名称：

  Elucidation of the Herbicidin Tailoring Pathway Offers Insights into Its Structural Diversity

  摘要：

  The biosynthetic gene clusters for herbicidins (hbc) and aureonuclemycin (anm) were identified in Streptomyces sp. KIB-027 and Streptomyces aureus, respectively. The roles of genes possibly involved in post-core-assembly steps in herbicidin biosynthesis in these clusters and a related her cluster were studied. Through systematic gene deletions, structural elucidation of the accumulated intermediates in the mutants, and in vitro verification of the encoded enzymes, the peripheral modification pathway for herbicidin biosynthesis is now fully established.

  DOI：

  10.1021/acs.orglett.9b00066
• 作为产物：
  描述：

  isobutyryl-coenzyme A 在 carboxymethylproline synthase 作用下， 以 水 为溶剂， 生成 coenzyme A 、 异丁酸
  参考文献：
  名称：

  来自巴豆酶超家族的羧甲基脯氨酸合酶的硫酯水解和 CC 键形成。

  摘要：

  DOI：

  10.1002/anie.200803906
• 作为试剂：
  描述：

  herbicidin G 在 coenzyme A 、 B₁₂-dependent radical S-adenosyl-L-methionine enzyme 、 herbicidins cluster contain methyltransferases HbcG 、 herbicidins cluster contain serine hydrolase HbcH 作用下， 以 aq. phosphate buffer 为溶剂， 反应 16.0h， 生成 除莠菌素 B
  参考文献：
  名称：

  Elucidation of the Herbicidin Tailoring Pathway Offers Insights into Its Structural Diversity

  摘要：

  The biosynthetic gene clusters for herbicidins (hbc) and aureonuclemycin (anm) were identified in Streptomyces sp. KIB-027 and Streptomyces aureus, respectively. The roles of genes possibly involved in post-core-assembly steps in herbicidin biosynthesis in these clusters and a related her cluster were studied. Through systematic gene deletions, structural elucidation of the accumulated intermediates in the mutants, and in vitro verification of the encoded enzymes, the peripheral modification pathway for herbicidin biosynthesis is now fully established.

  DOI：

  10.1021/acs.orglett.9b00066

文献信息

• Biosynthesis of the Allylmalonyl-CoA Extender Unit for the FK506 Polyketide Synthase Proceeds through a Dedicated Polyketide Synthase and Facilitates the Mutasynthesis of Analogues
  作者：SangJoon Mo、Dong Hwan Kim、Jong Hyun Lee、Je Won Park、Devi B. Basnet、Yeon Hee Ban、Young Ji Yoo、Shu-wei Chen、Sung Ryeol Park、Eun Ae Choi、Eunji Kim、Ying-Yu Jin、Sung-Kwon Lee、Ju Yeol Park、Yuan Liu、Mi Ok Lee、Keum Soon Lee、Sang Jun Kim、Dooil Kim、Byoung Chul Park、Sang-gi Lee、Ho Jeong Kwon、Joo-Won Suh、Bradley S. Moore、Si-Kyu Lim、Yeo Joon Yoon

  DOI：10.1021/ja108399b

  日期：2011.2.2

  engineered biosynthesis of novel allyl group-modified FK506 analogues, 36-fluoro-FK520 and 36-methyl-FK506, the latter of which exhibits improved neurite outgrowth activity. This unique feature of FK506 biosynthesis, in which a dedicated PKS provides an atypical extender unit for the main modular PKS, illuminates a new strategy for the combinatorial biosynthesis of designer macrolide scaffolds as well

  免疫抑制剂 FK506 的烯丙基部分在聚酮化合物中结构独特，对其有效的生物活性至关重要。在这里，我们基于对三个 FK506 基因簇的全面化学、生物化学和遗传询问，详细介绍了烯丙基丙二酰辅酶 A (CoA) 的生物合成途径，FK506 烯丙基是由 CoA 衍生而来。具有非规范结构域结构的离散聚酮合酶 (PKS) 可能与宿主的脂肪酸合酶途径协调，通过反式 2-戊烯酰基载体蛋白催化烯丙基丙二酰辅酶 A 的多步酶促反应。这一离散途径的表征促进了新型烯丙基修饰的 FK506 类似物、36-氟-FK520 和 36-甲基-FK506 的工程生物合成，后者表现出改善的神经突生长活性。 FK506 生物合成的这一独特特征（其中专用 PKS 为主模块化 PKS 提供非典型延伸单元）阐明了设计大环内酯支架和 FK506 类似物的组合生物合成的新策略。
• Synthesis and use of isotope-labelled substrates for a mechanistic study on human α-methylacyl-CoA racemase 1A (AMACR; P504S)
  作者：Daniel J. Darley、Danica S. Butler、Samuel J. Prideaux、Thomas W. Thornton、Abigail D. Wilson、Timothy J. Woodman、Michael D. Threadgill、Matthew D. Lloyd

  DOI：10.1039/b815396e

  日期：——

  α-Methylacyl-CoA racemase (AMACR) is an important enzyme for the metabolism of branched-chain lipids and drugs. The enzyme is over-expressed in prostate and other cancers. AMACR 1A, the major splice variant, was purified from recombinant E. colicells as a His-tag protein. Purified enzyme catalysed chiral inversion of both S- and R-2-methyldecanoyl-CoA, with an equilibrium constant of 1.09 ± 0.14 (2S/2R). Reactions with 2H-labelled substrate showed that loss of the α-proton was a prerequisite for chiral inversion. Reactions conducted in 2H2O indicated that reprotonation was not stereospecific. These results are the first mechanistic study on any recombinant mammalian α-methylacyl-CoA racemase.

  δ-甲基酰-CoA 消旋酶（AMACR）是支链脂质和药物代谢的一种重要酶。该酶在前列腺癌和其他癌症中过度表达。AMACR 1A 是主要的剪接变体，以 His 标记蛋白的形式从重组大肠杆菌中纯化。纯化的酶可催化 S- 和 R-2-methyldecanoyl-CoA 的手性反转，平衡常数为 1.09 ± 0.14 (2S/2R)。与 2H 标记底物的反应表明，δ-质子的损失是手性反转的先决条件。在 2H2O 中进行的反应表明，再质子化不是立体特异性的。这些结果是首次对任何重组哺乳动物δ-甲基酰-CoA 消旋酶进行机理研究。
• Molecular Basis for Converting (2S)-Methylsuccinyl-CoA Dehydrogenase into an Oxidase
  作者：Simon Burgener、Thomas Schwander、Elvira Romero、Marco Fraaije、Tobias Erb

  DOI：10.3390/molecules23010068

  日期：——

  Although flavoenzymes have been studied in detail, the molecular basis of their dioxygen reactivity is only partially understood. The members of the flavin adenosine dinucleotide (FAD)-dependent acyl-CoA dehydrogenase and acyl-CoA oxidase families catalyze similar reactions and share common structural features. However, both enzyme families feature opposing reaction specificities in respect to dioxygen. Dehydrogenases react with electron transfer flavoproteins as terminal electron acceptors and do not show a considerable reactivity with dioxygen, whereas dioxygen serves as a bona fide substrate for oxidases. We recently engineered (2S)-methylsuccinyl-CoA dehydrogenase towards oxidase activity by rational mutagenesis. Here we characterized the (2S)-methylsuccinyl-CoA dehydrogenase wild-type, as well as the engineered (2S)-methylsuccinyl-CoA oxidase, in detail. Using stopped-flow UV-spectroscopy and liquid chromatography-mass spectrometry (LC-MS) based assays, we explain the molecular base for dioxygen reactivity in the engineered oxidase and show that the increased oxidase function of the engineered enzyme comes at a decreased dehydrogenase activity. Our findings add to the common notion that an increased activity for a specific substrate is achieved at the expense of reaction promiscuity and provide guidelines for rational engineering efforts of acyl-CoA dehydrogenases and oxidases.

  尽管对黄酶类进行了详细研究，但对其二氧反应性的分子基础仅有部分了解。依赖黄素腺苷二核苷酸（FAD）的酰基-CoA 脱氢酶和酰基-CoA 氧化酶家族的成员催化类似的反应，并具有共同的结构特征。不过，这两个酶家族对二氧的反应特异性截然相反。脱氢酶与作为终端电子受体的电子传递黄蛋白反应，并不与二氧显示出相当大的反应性，而二氧则是氧化酶的真正底物。最近，我们通过合理诱变，设计出了具有氧化酶活性的 (2S)-methylsuccinyl-CoA dehydrogenase。在这里，我们对(2S)-甲基琥珀酰-CoA 脱氢酶野生型和改造的(2S)-甲基琥珀酰-CoA 氧化酶进行了详细表征。我们利用基于停流紫外光谱和液相色谱-质谱（LC-MS）的测定方法，解释了工程氧化酶中二氧反应性的分子基础，并表明工程酶氧化酶功能的增强是以脱氢酶活性的降低为代价的。我们的发现补充了一个普遍的观点，即特定底物活性的提高是以牺牲反应的杂合性为代价的，并为酰基-CoA 脱氢酶和氧化酶的合理工程化工作提供了指导。
• Molecular Identification of NAT8 as the Enzyme That Acetylates Cysteine S-Conjugates to Mercapturic Acids
  作者：Maria Veiga-da-Cunha、Donatienne Tyteca、Vincent Stroobant、Pierre J. Courtoy、Fred R. Opperdoes、Emile Van Schaftingen

  DOI：10.1074/jbc.m110.110924

  日期：2010.6

  Our goal was to identify the reaction catalyzed by NAT8 (N-acetyltransferase 8), a putative N-acetyltransferase homologous to the enzyme (NAT8L) that produces N-acetylaspartate in brain. The almost exclusive expression of NAT8 in kidney and liver and its predicted association with the endoplasmic reticulum suggested that it was cysteinyl-S-conjugate N-acetyltransferase, the microsomal enzyme that catalyzes the last step of mercapturic acid formation. In agreement, HEK293T extracts of cells overexpressing NAT8 catalyzed the N-acetylation of S-benzyl-L-cysteine and leukotriene E-4, two cysteine conjugates, but were inactive on other physiological amines or amino acids. Confocal microscopy indicated that NAT8 was associated with the endoplasmic reticulum. Neither of the two frequent single nucleotide polymorphisms found in NAT8, E104K nor F143S, changed the enzymatic activity or the expression of the protein by >= 2-fold, whereas a mutation (R149K) replacing an extremely conserved arginine suppressed the activity. Sequencing of genomic DNA and EST clones corresponding to the NAT8B gene, which resulted from duplication of the NAT8 gene in the primate lineage, disclosed the systematic presence of a premature stop codon at codon 16. Furthermore, truncated NAT8B and NAT8 proteins starting from the following methionine (Met-25) showed no cysteinyl-S-conjugate N-acetyltransferase activity when transfected in HEK293T cells. Taken together, these findings indicate that NAT8 is involved in mercapturic acid formation and confirm that NAT8B is an inactive gene in humans. NAT8 homologues are found in all vertebrate genomes, where they are often encoded by multiple, tandemly repeated genes as many other genes encoding xenobiotic metabolism enzymes.
• Elucidation of the Herbicidin Tailoring Pathway Offers Insights into Its Structural Diversity
  作者：Hai-Xue Pan、Zhang Chen、Tianfang Zeng、Wen-Bing Jin、Yujie Geng、Geng-Min Lin、Juan Zhao、Wei-Tao Li、Zijun Xiong、Sheng-Xiong Huang、Xin Zhai、Hung-wen Liu、Gong-Li Tang

  DOI：10.1021/acs.orglett.9b00066

  日期：2019.3.1

  The biosynthetic gene clusters for herbicidins (hbc) and aureonuclemycin (anm) were identified in Streptomyces sp. KIB-027 and Streptomyces aureus, respectively. The roles of genes possibly involved in post-core-assembly steps in herbicidin biosynthesis in these clusters and a related her cluster were studied. Through systematic gene deletions, structural elucidation of the accumulated intermediates in the mutants, and in vitro verification of the encoded enzymes, the peripheral modification pathway for herbicidin biosynthesis is now fully established.