S-citramalate

• 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: S-citramalate
• 英文别名: (2S)-2-hydroxy-2-methylbutanedioate
• 化学式: C₅H₆O₅
• 分子量: 146.1
• InChiKey: XFTRTWQBIOMVPK-YFKPBYRVSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  S-citramalate 生成 乙酸盐 、 piruvate
  参考文献：
  名称：

  Diversity of Function in the Isocitrate Lyase Enzyme Superfamily:  The Dianthus caryophyllus Petal Death Protein Cleaves α-Keto and α-Hydroxycarboxylic Acids

  摘要：

  The work described in this paper was carried Out to define the chemical function a new member of the isocitrate lyase enzyme family derived from the flowering plant Dianthus caryophyllus. This protein (Swiss-Prot entry Q05957) is synthesized in the senescent flower petals and is named the "petal death protein" or "PDP". On the basis of an analysis of the structural contexts of sequence markers common to the C-C bond lyases of the isocitrate lyase/phosphoenolpyruvate mutase superfamily, a substrate screen that employed a (2R)-malate core Structure was designed. Accordingly, stereochemically defined C(2)and C(3)-substituted malates were synthesized and tested as Substrates for PDP-catalyzed cleavage of the C(2)-C(3) bond. The screen identified (2R)-ethyl, (3S)-methylmalate, and oxaloacetate [likely to bind as the hydrate, C(2)(OH)(2) gem-diol] as the most active Substrates (for each, k(cat)/K-m = 2 x 10(4) M-1 s(-1)). In contrast to the stringent substrate specificities previously observed for the Escherichia coli isocitrate and 2-methylisocitrate lyases, the PDP tolerated hydrogen, methyl, and to a much lesser extent acetate substituents at the C(3) position (S configuration only) and hydoxyl, methyl, ethyl, propyl, and to a much lesser extent isobutyl substituents at C(2) (R configuration only). It is hypothesized that PDP functions in oxalate production in Ca2+ sequestering and/or in carbon scavenging from alpha-hydroxycarboxylate catabolites during the biochemical transition accompanying petal senescence.

  DOI：

  10.1021/bi051776l
• 作为产物：
  描述：

  mesaconate 在 PfFHΔ40 作用下， 生成 S-citramalate
  参考文献：
  名称：

  富马酸疟原虫水合酶的生化特性和必要性。

  摘要：

  疟疾的病原体恶性疟原虫（Pf）具有含铁硫簇的I类富马酸盐水合酶（FH），可催化富马酸盐向苹果酸的相互转化，这是三羧酸循环中众所周知的反应。在人类中，相同的反应由II类FH催化，它与来自富马酸疟原虫的I类酶没有序列或结构同源性，在寄生虫中作为AMP合成的副产物大量产生，并由FH转化为苹果酸然后用于关键代谢产物草酰乙酸，天冬氨酸和丙酮酸的生成。先前的研究已经确定FH反应是恶性疟原虫必不可少的，但是缺乏PfFH的生化特性，可能为开发特定的抑制剂提供线索。这里，我们报告了纯化的重组PfFH的动力学特性，大肠杆菌中fh缺乏的功能互补以及寄生虫中的线粒体定位。我们发现底物类似物巯基琥珀酸是一种有效的PfFH抑制剂，Ki值在纳摩尔范围内。将转染子导入BALB / c小鼠后，无法在伯氏疟原虫中敲除fh基因。但是，当以C57BL / 6小鼠为宿主时，fh基因敲除是成功的，这表明fh基因对寄生虫的必要性取决于小鼠品系。将转染子导入BALB

  DOI：

  10.1074/jbc.m117.816298

文献信息

• Properties of Succinyl-Coenzyme A: <scp>l</scp> -Malate Coenzyme A Transferase and Its Role in the Autotrophic 3-Hydroxypropionate Cycle of <i>Chloroflexus aurantiacus</i>
  作者：Silke Friedmann、Astrid Steindorf、Birgit E. Alber、Georg Fuchs

  DOI：10.1128/jb.188.7.2646-2655.2006

  日期：2006.4

  The 3-hydroxypropionate cycle has been proposed to operate as the autotrophic CO ₂ fixation pathway in the phototrophic bacterium Chloroflexus aurantiacus . In this pathway, acetyl coenzyme A (acetyl-CoA) and two bicarbonate molecules are converted to malate. Acetyl-CoA is regenerated from malyl-CoA by l -malyl-CoA lyase. The enzyme forming malyl-CoA, succinyl-CoA: l -malate coenzyme A transferase, was purified. Based on the N-terminal amino acid sequence of its two subunits, the corresponding genes were identified on a gene cluster which also contains the gene for l -malyl-CoA lyase, the subsequent enzyme in the pathway. Both enzymes were severalfold up-regulated under autotrophic conditions, which is in line with their proposed function in CO ₂ fixation. The two CoA transferase genes were cloned and heterologously expressed in Escherichia coli , and the recombinant enzyme was purified and studied. Succinyl-CoA: l -malate CoA transferase forms a large (αβ) _n complex consisting of 46- and 44-kDa subunits and catalyzes the reversible reaction succinyl-CoA + l -malate → succinate + l -malyl-CoA. It is specific for succinyl-CoA as the CoA donor but accepts l -citramalate instead of l -malate as the CoA acceptor; the corresponding d -stereoisomers are not accepted. The enzyme is a member of the class III of the CoA transferase family. The demonstration of the missing CoA transferase closes the last gap in the proposed 3-hydroxypropionate cycle.

  摘要 有人提出 3-羟基丙酸循环作为自养型 CO 2 固定途径。 的自养二氧化碳固定途径。 .在这一途径中，乙酰辅酶 A（乙酰-CoA）和两个碳酸氢分子被转化为苹果酸。乙酰辅酶 A 通过以下途径从苹果酸中再生 l -丙二酸裂解酶从丙二酸中再生。形成丙二酰-CoA、琥珀酰-CoA 的酶： l -丙二酸辅酶 A 转移酶。根据其两个亚基的 N 端氨基酸序列，在一个基因簇上确定了相应的基因，该基因簇还包括 l -丙二酰-CoA：l -丙二酸辅酶 A 转移酶的基因。 l -丙二酰-CoA 裂解酶的基因。在自养条件下，这两种酶都有数倍的上调，这与它们在 CO 2 固定的功能。这两种 CoA 转移酶基因被克隆并异源表达于 大肠杆菌 对重组酶进行了纯化和研究。琥珀酰-CoA： l 琥珀酰-CoA：l-苹果酸 CoA 转移酶形成一个大的 (αβ) n 复合物，催化琥珀酰-CoA + l -苹果酸的可逆反应。 l -丙二酸 → 琥珀酸 + l -丙二酸。它专门以琥珀酰-CoA 作为 CoA 供体，但也接受 l -柠檬醛酸，而不是 l -丙二酸作为 CoA 受体；相应的 d -立体异构体不被接受。该酶属于 CoA 转移酶家族第三类。缺失的 CoA 转移酶的发现填补了 3-羟基丙酸循环中的最后一个空白。
• Wang C.C.; Barker H.A., J Biol Chem, 1969, 0021-9258, 2516-26
  作者：Wang C.C.、Barker H.A.

  DOI：——

  日期：——
• Blair A.H.; Barker H.A., J Biol Chem, 1966, 0021-9258, 400-8
  作者：Blair A.H.、Barker H.A.

  DOI：——

  日期：——
• Biochemical characterization and essentiality of fumarate hydratase
  作者：Vijay Jayaraman、Arpitha Suryavanshi、Pavithra Kalale、Jyothirmai Kunala、Hemalatha Balaram

  DOI：10.1074/jbc.m117.816298

  日期：2018.4

  of malaria, has an iron-sulfur cluster-containing class I fumarate hydratase (FH) that catalyzes the interconversion of fumarate to malate, a well-known reaction in the tricarboxylic acid cycle. In humans, the same reaction is catalyzed by class II FH that has no sequence or structural homology with the class I enzyme from Plasmodium Fumarate is generated in large quantities in the parasite as a by-product

  疟疾的病原体恶性疟原虫（Pf）具有含铁硫簇的I类富马酸盐水合酶（FH），可催化富马酸盐向苹果酸的相互转化，这是三羧酸循环中众所周知的反应。在人类中，相同的反应由II类FH催化，它与来自富马酸疟原虫的I类酶没有序列或结构同源性，在寄生虫中作为AMP合成的副产物大量产生，并由FH转化为苹果酸然后用于关键代谢产物草酰乙酸，天冬氨酸和丙酮酸的生成。先前的研究已经确定FH反应是恶性疟原虫必不可少的，但是缺乏PfFH的生化特性，可能为开发特定的抑制剂提供线索。这里，我们报告了纯化的重组PfFH的动力学特性，大肠杆菌中fh缺乏的功能互补以及寄生虫中的线粒体定位。我们发现底物类似物巯基琥珀酸是一种有效的PfFH抑制剂，Ki值在纳摩尔范围内。将转染子导入BALB / c小鼠后，无法在伯氏疟原虫中敲除fh基因。但是，当以C57BL / 6小鼠为宿主时，fh基因敲除是成功的，这表明fh基因对寄生虫的必要性取决于小鼠品系。将转染子导入BALB
• Diversity of Function in the Isocitrate Lyase Enzyme Superfamily:  The<i> Dianthus caryophyllus</i> Petal Death Protein Cleaves α-Keto and α-Hydroxycarboxylic Acids
  作者：Zhibing Lu、Xiaohua Feng、Ling Song、Ying Han、Alexander Kim、Osnat Herzberg、William R. Woodson、Brian M. Martin、Patrick S. Mariano、Debra Dunaway-Mariano

  DOI：10.1021/bi051776l

  日期：2005.12.1

  The work described in this paper was carried Out to define the chemical function a new member of the isocitrate lyase enzyme family derived from the flowering plant Dianthus caryophyllus. This protein (Swiss-Prot entry Q05957) is synthesized in the senescent flower petals and is named the "petal death protein" or "PDP". On the basis of an analysis of the structural contexts of sequence markers common to the C-C bond lyases of the isocitrate lyase/phosphoenolpyruvate mutase superfamily, a substrate screen that employed a (2R)-malate core Structure was designed. Accordingly, stereochemically defined C(2)and C(3)-substituted malates were synthesized and tested as Substrates for PDP-catalyzed cleavage of the C(2)-C(3) bond. The screen identified (2R)-ethyl, (3S)-methylmalate, and oxaloacetate [likely to bind as the hydrate, C(2)(OH)(2) gem-diol] as the most active Substrates (for each, k(cat)/K-m = 2 x 10(4) M-1 s(-1)). In contrast to the stringent substrate specificities previously observed for the Escherichia coli isocitrate and 2-methylisocitrate lyases, the PDP tolerated hydrogen, methyl, and to a much lesser extent acetate substituents at the C(3) position (S configuration only) and hydoxyl, methyl, ethyl, propyl, and to a much lesser extent isobutyl substituents at C(2) (R configuration only). It is hypothesized that PDP functions in oxalate production in Ca2+ sequestering and/or in carbon scavenging from alpha-hydroxycarboxylate catabolites during the biochemical transition accompanying petal senescence.