(3E)-hexenoyl-CoA

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (3E)-hexenoyl-CoA
• 英文别名: [(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-2-[[[[(3R)-4-[[3-[2-[(E)-hex-3-enoyl]sulfanylethylamino]-3-oxopropyl]amino]-3-hydroxy-2,2-dimethyl-4-oxobutoxy]-oxidophosphoryl]oxy-oxidophosphoryl]oxymethyl]-4-hydroxyoxolan-3-yl] phosphate
• 化学式: C27H40N7O17P3S-4
• 分子量: 859.6
• InChiKey: SKDDJNFRAZIJIG-SYLRIUJSSA-J

计算性质

• 辛醇/水分配系数(LogP)：
  -4.6
• 重原子数：
  55
• 可旋转键数：
  22
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  400
• 氢给体数：
  5
• 氢受体数：
  22

反应信息

• 作为反应物：
  描述：

  (3E)-hexenoyl-CoA 生成 trans-2-Hexenoyl-CoA
  参考文献：
  名称：

  Organization of the multifunctional enzyme type 1: interaction between N- and C-terminal domains is required for the hydratase-1/isomerase activity

  摘要：

  大鼠过氧化物酶体多功能酶 1 型（perMFE-1）是一种 β 氧化单体蛋白。根据氨基酸序列与数据库中同源蛋白的比较以及氢化酶-1/异构酶（H1/I）和（3S）-羟基乙酰-CoA 脱氢酶（HAD）的结构数据，我们定义了 perMFE-1 的五个功能域（A、B、C、D 和 E）。结构域 A（残基 1-190）包含 H1/I 折叠结构，可催化 2-烯酰基-CoAhydratase-1 和 Δ3-Δ2- 烯酰基-CoA 异构酶反应。结构域 B（残基 191-280）将结构域 A 与（3S）-脱氢酶区域连接起来，后者包括结构域 C（残基 281-474）和结构域 D（残基 480-583）。结构域 C 和 D 分别具有单功能 HAD 的二核苷酸结合结构域和二聚化结构域的特征。结构域 E（残基 584-722）与 perMFE-1 的结构域 D 序列相似，这表明它是通过部分基因复制进化而来的。用改造过的 perMFE-1 变体进行的实验表明，结构域 A 的 H1/I 能力需要与结构域 D 和 E 进行稳定的相互作用。据推测，perMFE-1 中极端 C 端结构域 E 具有以下三种功能：(i) 参与 N 端折叠成具有功能性的 H1/I 折叠；(ii) 通过与结构域 D 的相互作用稳定脱氢结构域；(iii) 通过其 C 端三肽将 perMFE-1 定位于过氧化物酶体。

  DOI：

  10.1042/bj20020292
• 作为产物：
  描述：

  trans,trans-2,4-hexadienoyl-CoA(4-) 、 氢(+1)阳离子 、 NADPH(4-) 生成 (3E)-hexenoyl-CoA 、 NADP⁺
  参考文献：
  名称：

  Characterisation of human peroxisomal 2,4-dienoyl-CoA reductase1The sequence was deposited in the EMBL database (AJ293009).12During the preparation of this manuscript, the sequence of clone LA61-359F1 was finalised (AL023881 version 24) and an ORF was deduced which was identical to the cloned pDCR cDNA.2

  摘要：

  Based on the primary structure of the rat peroxisomal 2,4-dienoyl-CoA reductase (M. Fransen, P.P. Van Veldhoven, S. Subramani, Biochem. J. 340 (1999) 561-568), the cDNA of the human counterpart was cloned. It contained an open reading frame of 878 bases encoding a protein of 291 amino acids (calculated molecular mass 30 778 Da), being 83% identical to the rat reductase. The gene, encompassing nine exons, is located at chromosome 16p13. Bacterially expressed poly(His)tagged reductase was active not only towards short and medium chain 2,4-dienoyl-CoAs, but also towards 2,4,7,10,13,16,19-docosaheptaenoyl-CoA. Hence, the reductase does not seem to constitute a rate limiting step in the peroxisomal degradation of docosahexaenoic acid. The reduction of docosaheptaenoyl-CoA, however, was severely decreased in the presence of albumin. (C) 2001 Elsevier Science B.V. Al rights reserved.

  DOI：

  10.1016/s1388-1981(01)00141-x

文献信息

• Characterisation of human peroxisomal 2,4-dienoyl-CoA reductase1The sequence was deposited in the EMBL database (AJ293009).12During the preparation of this manuscript, the sequence of clone LA61-359F1 was finalised (AL023881 version 24) and an ORF was deduced which was identical to the cloned pDCR cDNA.2
  作者：Katelijne De Nys、Els Meyhi、Guy P Mannaerts、Marc Fransen、Paul P Van Veldhoven

  DOI：10.1016/s1388-1981(01)00141-x

  日期：2001.8

  Based on the primary structure of the rat peroxisomal 2,4-dienoyl-CoA reductase (M. Fransen, P.P. Van Veldhoven, S. Subramani, Biochem. J. 340 (1999) 561-568), the cDNA of the human counterpart was cloned. It contained an open reading frame of 878 bases encoding a protein of 291 amino acids (calculated molecular mass 30 778 Da), being 83% identical to the rat reductase. The gene, encompassing nine exons, is located at chromosome 16p13. Bacterially expressed poly(His)tagged reductase was active not only towards short and medium chain 2,4-dienoyl-CoAs, but also towards 2,4,7,10,13,16,19-docosaheptaenoyl-CoA. Hence, the reductase does not seem to constitute a rate limiting step in the peroxisomal degradation of docosahexaenoic acid. The reduction of docosaheptaenoyl-CoA, however, was severely decreased in the presence of albumin. (C) 2001 Elsevier Science B.V. Al rights reserved.
• Palosaari P.M.; Hiltunen J.K., J Biol Chem, 1990, 0021-9258, 2446-9
  作者：Palosaari P.M.、Hiltunen J.K.

  DOI：——

  日期：——
• Organization of the multifunctional enzyme type 1: interaction between N- and C-terminal domains is required for the hydratase-1/isomerase activity
  作者：Tiila-Riikka KIEMA、Jukka P. TASKINEN、Päivi L. PIRILÄ、Kari T. KOIVURANTA、Rik K. WIERENGA、J. Kalervo HILTUNEN

  DOI：10.1042/bj20020292

  日期：2002.10.15

  Rat peroxisomal multifunctional enzyme type 1 (perMFE-1) is a monomeric protein of β-oxidation. We have defined five functional domains (A, B, C, D and E) in the perMFE-1 based on comparison of the amino acid sequence with homologous proteins from databases and structural data of the hydratase-1/isomerases (H1/I) and (3S)-hydroxyacyl-CoA dehydrogenases (HAD). Domain A (residues 1—190) comprises the H1/I fold and catalyses both 2-enoyl-CoA hydratase-1 and Δ3—Δ2-enoyl-CoA isomerase reactions. Domain B (residues 191—280) links domain A to the (3S)-dehydrogenase region, which includes both domain C (residues 281—474) and domain D (residues 480—583). Domains C and D carry features of the dinucleotide-binding and the dimerization domains of monofunctional HADs respectively. Domain E (residues 584—722) has sequence similarity to domain D of the perMFE-1, which suggests that it has evolved via partial gene duplication. Experiments with engineered perMFE-1 variants demonstrate that the H1/I competence of domain A requires stabilizing interactions with domains D and E. The variant His-perMFE (residues 288—479)Δ, in which the domain C is deleted, is stable and has hydratase-1 activity. It is proposed that the extreme C-terminal domain E in perMFE-1 serves the following three functions: (i) participation in the folding of the N-terminus into a functionally competent H1/I fold, (ii) stabilization of the dehydrogenation domains by interaction with the domain D and (iii) the targeting of the perMFE-1 to peroxisomes via its C-terminal tripeptide.

  大鼠过氧化物酶体多功能酶 1 型（perMFE-1）是一种 β 氧化单体蛋白。根据氨基酸序列与数据库中同源蛋白的比较以及氢化酶-1/异构酶（H1/I）和（3S）-羟基乙酰-CoA 脱氢酶（HAD）的结构数据，我们定义了 perMFE-1 的五个功能域（A、B、C、D 和 E）。结构域 A（残基 1-190）包含 H1/I 折叠结构，可催化 2-烯酰基-CoAhydratase-1 和 Δ3-Δ2- 烯酰基-CoA 异构酶反应。结构域 B（残基 191-280）将结构域 A 与（3S）-脱氢酶区域连接起来，后者包括结构域 C（残基 281-474）和结构域 D（残基 480-583）。结构域 C 和 D 分别具有单功能 HAD 的二核苷酸结合结构域和二聚化结构域的特征。结构域 E（残基 584-722）与 perMFE-1 的结构域 D 序列相似，这表明它是通过部分基因复制进化而来的。用改造过的 perMFE-1 变体进行的实验表明，结构域 A 的 H1/I 能力需要与结构域 D 和 E 进行稳定的相互作用。据推测，perMFE-1 中极端 C 端结构域 E 具有以下三种功能：(i) 参与 N 端折叠成具有功能性的 H1/I 折叠；(ii) 通过与结构域 D 的相互作用稳定脱氢结构域；(iii) 通过其 C 端三肽将 perMFE-1 定位于过氧化物酶体。
• Structure and Reactivity of Human Mitochondrial 2,4-Dienoyl-CoA Reductase
  作者：Magnus S. Alphey、Wenhua Yu、Emma Byres、Ding Li、William N. Hunter

  DOI：10.1074/jbc.m411069200

  日期：2005.1

  Fatty acid catabolism by beta-oxidation mainly occurs in mitochondria and to a lesser degree in peroxisomes. Polyunsaturated fatty acids are problematic for beta-oxidation, because the enzymes directly involved are unable to process all the different double bond conformations and combinations that occur naturally. In mammals, three accessory proteins circumvent this problem by catalyzing specific isomerization and reduction reactions. Central to this process is the NADPH-dependent 2,4-dienoyl-CoA reductase. We present high resolution crystal structures of human mitochondrial 2,4-dienoyl-CoA reductase in binary complex with cofactor, and the ternary complex with NADP(+) and substrate trans-2,trans-4-dienoyl-CoA at 2.1 and 1.75 Angstrom resolution, respectively. The enzyme, a homotetramer, is a short-chain dehydrogenase/reductase with a distinctive catalytic center. Close structural similarity between the binary and ternary complexes suggests an absence of large conformational changes during binding and processing of substrate. The site of catalysis is relatively open and placed beside a flexible loop thereby allowing the enzyme to accommodate and process a wide range of fatty acids. Seven single mutants were constructed, by site-directed mutagenesis, to investigate the function of selected residues in the active site thought likely to either contribute to the architecture of the active site or to catalysis. The mutant proteins were overexpressed, purified to homogeneity, and then characterized. The structural and kinetic data are consistent and support a mechanism that derives one reducing equivalent from the cofactor, and one from solvent. Key to the acquisition of a solvent-derived proton is the orientation of substrate and stabilization of a dienolate intermediate by Tyr-199, Asn-148, and the oxidized nicotinamide.