o-succinylbenzoate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: o-succinylbenzoate
• 英文别名: 2-(3-Carboxylatopropanoyl)benzoate
• 化学式: C₁₁H₈O₅
• 分子量: 220.182
• InChiKey: YIVWQNVQRXFZJB-UHFFFAOYSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  97.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  o-succinylbenzoate 、 辅酶 A 在 Escherichia coli MenC enzyme 、 Escherichia coli MenE enzyme 、 5’-三磷酸腺苷 、 magnesium chloride 作用下， 反应 0.13h， 生成
  参考文献：
  名称：

  A Bicarbonate Cofactor Modulates 1,4-Dihydroxy-2-naphthoyl-Coenzyme A Synthase in Menaquinone Biosynthesis of Escherichia coli

  摘要：

  1,4-Dihydroxy-2-naphthoyl coenzyme A (DHNA-CoA) synthase is a typical crotonase-fold protein catalyzing an intramolecular Claisen condensation in the menaquinone biosynthetic pathway. We have characterized this enzyme from Escherichia coli and found that it is activated by bicarbonate in a concentration-dependent manner. The bicarbonate binding site has been identified in the crystal structure of a virtually identical ortholog (96.8% sequence identity) from Salmonella typhimurium through comparison with a bicarbonate-insensitive orthologue. Kinetic properties of the enzyme and its site-directed mutants of the bicarbonate binding site indicate that the exogenous bicarbonate anion is essential to the enzyme activity. With this essential catalytic role, the simple bicarbonate anion is an enzyme cofactor, which is usually a small organic molecule derived from vitamins, a metal ion, or a metal-containing polyatomic anionic complex. This finding leads to classification of the DHNA-CoA synthases into two evolutionarily conserved subfamilies: type I enzymes that are bicarbonate-dependent and contain a conserved glycine at the bicarbonate binding site; and type II enzymes that are bicarbonate-independent and contain a conserved aspartate at the position similar to the enzyme-bound bicarbonate. In addition, the unique location of the enzyme-bound bicarbonate allows it to be proposed as a catalytic base responsible for abstraction of the alpha-proton of the thioester substrate in the enzymatic reaction, suggesting a unified catalytic mechanism for all DHNA-CoA synthases.

  DOI：

  10.1074/jbc.m110.147702
• 作为产物：
  描述：

  (1R,6R)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate 在 Escherichia coli MenC enzyme 、 5’-三磷酸腺苷 、 辅酶 A 、 magnesium chloride 作用下， 反应 0.25h， 生成 o-succinylbenzoate
  参考文献：
  名称：

  A Bicarbonate Cofactor Modulates 1,4-Dihydroxy-2-naphthoyl-Coenzyme A Synthase in Menaquinone Biosynthesis of Escherichia coli

  摘要：

  1,4-Dihydroxy-2-naphthoyl coenzyme A (DHNA-CoA) synthase is a typical crotonase-fold protein catalyzing an intramolecular Claisen condensation in the menaquinone biosynthetic pathway. We have characterized this enzyme from Escherichia coli and found that it is activated by bicarbonate in a concentration-dependent manner. The bicarbonate binding site has been identified in the crystal structure of a virtually identical ortholog (96.8% sequence identity) from Salmonella typhimurium through comparison with a bicarbonate-insensitive orthologue. Kinetic properties of the enzyme and its site-directed mutants of the bicarbonate binding site indicate that the exogenous bicarbonate anion is essential to the enzyme activity. With this essential catalytic role, the simple bicarbonate anion is an enzyme cofactor, which is usually a small organic molecule derived from vitamins, a metal ion, or a metal-containing polyatomic anionic complex. This finding leads to classification of the DHNA-CoA synthases into two evolutionarily conserved subfamilies: type I enzymes that are bicarbonate-dependent and contain a conserved glycine at the bicarbonate binding site; and type II enzymes that are bicarbonate-independent and contain a conserved aspartate at the position similar to the enzyme-bound bicarbonate. In addition, the unique location of the enzyme-bound bicarbonate allows it to be proposed as a catalytic base responsible for abstraction of the alpha-proton of the thioester substrate in the enzymatic reaction, suggesting a unified catalytic mechanism for all DHNA-CoA synthases.

  DOI：

  10.1074/jbc.m110.147702

文献信息

• Evolution of Enzymatic Activity in the Enolase Superfamily:  Structure of <i>o</i>-Succinylbenzoate Synthase from <i>Escherichia coli </i>in Complex with Mg²⁺ and <i>o</i>-Succinylbenzoate^,
  作者：Thomas B. Thompson、James B. Garrett、Erika A. Taylor、R. Meganathan、John A. Gerlt、Ivan Rayment

  DOI：10.1021/bi000855o

  日期：2000.9.1

  positioned to function as acid/base catalysts in the dehydration reaction. Few hydrogen bonding or electrostatic interactions are involved in the binding of OSB to the active site; instead, most of the interactions between OSB and the protein are either indirect via water molecules or via hydrophobic interactions. As a result, evolution of both the shape and the volume of the active site should be subject

  来自大肠杆菌的邻琥珀酰苯甲酸酯合酶（OSBS）的无配体（apo）和Mg（2 +）*邻琥珀酰苯甲酸酯（OSB）产品复合物的X射线结构已分别解析为1.65和1.77 A分辨率。通过在空间群P2（1）2（1）2（1）中进行多个同构置换来解决apo OSBS的结构；通过分子置换在空间群P2（1）2（1）2中解决了Mg（2 +）* OSB配合物的结构。OSBS的两个结构域折叠与烯醇酶超家族其他成员的结构域折叠相似：混合的α/β封端结构域由多肽的N-和C-末端的片段和较大的（β/ alpha）（ 7）beta桶域。在载脂蛋白OSBS的结构中发现了两个无序区域：（i）α/β结构域中前两个β链之间的环；（ii）桶形域中的第一对片-螺旋对。这些区域在具有Mg（2 +）* OSB的产品复合物中排序。如预期的那样，Mg（2 +）* OSB对结合在桶状结构域的C末端。产品中琥珀酸苯基酯组分的电子密度是明确定义的；
• Evolution of Enzymatic Activity in the Enolase Superfamily:  Functional Studies of the Promiscuous <i>o</i>-Succinylbenzoate Synthase from <i>Amycolatopsis</i>
  作者：Erika A. Taylor Ringia、James B. Garrett、James B. Thoden、Hazel M. Holden、Ivan Rayment、John A. Gerlt

  DOI：10.1021/bi035815+

  日期：2004.1.1

  o-Succinylbenzoate synthase (OSBS) from Amycolatopsis, a member of the enolase superfamily, catalyzes the Mn2+-dependent exergonic dehydration of 2-succinyl-6R-hydroxy-2,4-cyclohexadiene-1R-carboxylate (SHCHC) to 4-(2'-carboxylphenyl)-4-oxobutyrate (o-succinylbenzoate or OSB) in the menaquinone biosynthetic pathway. This enzyme first was identified as an N-acylamino acid racemase (NAAAR), with the

  烯醇化酶超家族成员Amycolatopsis的邻琥珀酰苯甲酸酯合酶（OSBS）催化2-琥珀酰-6R-羟基-2,4-环己二烯-1R-羧酸盐（SHCHC）的Mn2 +依赖于能级脱水（SHCHC）生成4-（2甲萘醌生物合成途径中的'-羧基苯基）-4-氧代丁酸酯（邻琥珀酰苯甲酸酯或OSB）。该酶首先被鉴定为N-酰基氨基酸消旋酶（NAAAR），最佳底物是N-乙酰甲硫氨酸的对映异构体。该实验室随后发现，该蛋白是OSBS反应的更好的催化剂，脱水的k（cat）/ K（M）值为2.5 x 10（5）M（-1）s（-1） ，大大超过了以N-乙酰甲硫氨酸的对映体为底物进行的1,1质子转移所需要的3.1 x 10（2）M（-1）s（-1）[Palmer，DR，Garrett，JB，Sharma，V. ，R。Meganathan，Babbitt，PC，和Gerlt，JA（1999）Biochemistry 38，4
• Evolution of Enzymatic Activity in the Enolase Superfamily:  Structural and Mutagenic Studies of the Mechanism of the Reaction Catalyzed by <i>o-</i>Succinylbenzoate Synthase from <i>Escherichia coli</i>^,
  作者：Vadim A. Klenchin、Erika A. Taylor Ringia、John A. Gerlt、Ivan Rayment

  DOI：10.1021/bi035545v

  日期：2003.12.1

  dehydration proceed via a syn stereochemical course. The side chain of Arg 133 is pointed out of the active site so that it cannot function as a general base, whereas in the wild-type enzyme complexed with Mg(2+).OSB, the side chain of Lys 133 is appropriately positioned to function as the only acid/base catalyst in the syn dehydration. The epsilon-ammonium group of Lys 235 forms a cation-pi interaction with

  烯醇酶超家族成员大肠埃希氏大肠杆菌的邻琥珀酰苯甲酸酯合酶（OSBS）催化甲基萘醌生物合成途径中的能级脱水反应，其中2-琥珀酰基-6-羟基-2,4-环己二烯-1-羧酸盐（SHCHC）被转化为4-（2'-羧苯基）-4-氧代丁酸酯（邻琥珀酰苯甲酸酯或OSB）。我们之前对Mg（2 +）。OSB复合物的结构研究表明，OSBS是超家族的粘液内酯化酶亚组的成员：必需的Mg（2+）与第三，第四末端的配体羧基化，以及（beta / alpha）（7）beta-barrel催化结构域的第五个beta链，并且OSB产物位于第二个beta链末端的Lys 133和第二个beta链末端的Lys 235之间。第六β链[汤普森，TB，加勒特，JB，泰勒，EA，梅加纳森，R。，Gerlt，JA和Rayment，I。（2000）Biochemistry 39，10662-76]。Lys 133和Lys 235分别被Ala，S
• Menaquinone (vitamin K2) biosynthesis: cloning, nucleotide sequence, and expression of the menC gene from Escherichia coli
  作者：V Sharma、R Meganathan、M E Hudspeth

  DOI：10.1128/jb.175.15.4917-4921.1993

  日期：1993.8

  The benzenoid aromatic compound o-succinylbenzoic acid is formed by dehydration of the prearomatic compound 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylic acid by the enzyme o-succinylbenzoate synthase, encoded by the menC gene. A 1.3-kb PstI-PvuII fragment was found to complement the menC mutation. The complete nucleotide sequence of this fragment revealed a single open reading frame of 954 bp capable of encoding a 35-kDa protein. A consensus sequence for a ribosomal binding site but no promoter consensus sequences were found. However, the first base of the initiating codon of this open reading frame overlaps the upstream menB gene termination codon, suggesting an operon-like organization for these genes. Consistent with this suggestion, the menB promoter can initiate transcription of the menC gene.

  邻苯二甲酸酐类芳香化合物o-琥珀酰基苯甲酸是由o-琥珀酰基苯甲酸合成酶(o-succinylbenzoate synthase)所催化的2-琥珀酰基-6-羟基-2,4-环己二烯-1-羧酸的脱水反应而形成的，该酶由menC基因编码。发现一个1.3kb的PstI-PvuII片段可以补全menC突变。该片段的完整核苷酸序列显示了一个能够编码35kDa蛋白质的单个开放阅读框架，长度为954bp。没有发现启动子共识序列，但是该开放阅读框架的起始密码子的第一个碱基与上游的menB基因终止密码子重叠，表明这些基因具有类似操纵子的组织结构。与这个建议相一致，menB启动子可以启动menC基因的转录。
• 4-(2′-Carboxyphenyl)-4-oxobutyryl Coenzyme A Ester, an Intermediate in Vitamin K₂ (Menaquinone) Biosynthesis
  作者：Rainer Kolkmann、Eckhard Leistner

  DOI：10.1515/znc-1987-11-1212

  日期：1987.12.1

  Enzyme preparations from Mycobacterium phlei, Escherichia coli and Galium mollugo cell suspension cultures were incubated in the presence of 4-(2′-carboxyphenyl)-4-oxobutyrate (i.e. o- succinylbenzoic acid. OSB. 1). ATP. coenzyme A and Mg2+. The main product isolated from the incubation mixture was 4-(2′-carboxyphenyl)-4-oxobutyryl coenzyme A ester (2) as determined by comparison with synthetic coenzyme

  在4-(2'-羧基苯基)-4-氧代丁酸(即邻琥珀酰苯甲酸。OSB.1)存在下，培养来自草分枝杆菌、大肠杆菌和软体动物镓细胞悬浮培养物的酶制剂。三磷酸腺苷。辅酶 A 和 Mg2+。从孵育混合物中分离的主要产物是 4-(2'-羧基苯基)-4-氧代丁酰基辅酶 A 酯 (2)，通过与合成辅酶 A 酯的比较确定。合成的和酶促形成的 4-(2'-羧基苯基)-4-氧代丁酰基辅酶 A 酯 (2) 被证明可以酶促转化为维生素 K2 生物合成的中间体，即。1.4-二羟基-2'-萘甲酸 (5)。还观察到 2-(3'-羧基丙酰基)苯甲酰基辅酶 A 酯 (3) 和 4-(2'-羧基苯基)-4-氧代丁酰基-二-辅酶 A 酯 (4) 的酶促形成。然而，它们以少量出现。