2-oxopropyl-CoM(1-)

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磺酸及其衍生物
• 英文名称: 2-oxopropyl-CoM(1-)
• 英文别名: 2-(2-oxopropylsulfanyl)ethanesulfonate
• 化学式: C₅H₉O₄S₂
• 分子量: 197.256
• InChiKey: CRNXHFXAXBWIRH-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  11
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  108
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  二氧化碳 、 2-oxopropyl-CoM(1-) 在 2-ketopropyl-coenzyme M carboxylase/oxidoreductase 、 recombinant Rhodobacter sp. DSMZ 12077 β-hydroxybutyrate dehydrogenase 、 potassium hydrogencarbonate 、 还原型辅酶Ⅰ 、 1,4-二巯基-2,3-丁二醇 作用下， 生成 2-mercaptoethanesulfonate 、 acetoacetic acid anion
  参考文献：
  名称：

  辅酶 M 类似物 2-溴乙磺酸酯抑制脂肪族环氧化物羧化的机制。

  摘要：

  丙烯氧化形成的环氧丙烷的细菌代谢使用非典型辅酶辅酶 M（CoM，2-巯基乙磺酸盐）作为环氧化物开环的亲核试剂和中间体的载体，在三个过程中经过脱氢、还原裂解和羧化形成乙酰乙酸盐。 -步代谢途径。2-酮丙基-CoM 羧化酶/氧化还原酶 (2-KPCC)，该途径的末端酶，是二硫化物氧化还原酶家族中唯一已知的羧化酶成员。在目前的工作中，CoM 类似物 2-溴乙磺酸 (BES) 被证明是 2-KPCC 和羟丙基-CoM 脱氢酶的可逆抑制剂，但不是环氧烷烃：CoM 转移酶的可逆抑制剂。进一步的研究表明，BES 是二硫苏糖醇还原的 2-KPCC 的时间依赖性灭活剂，其中氧化还原活性半胱氨酸呈游离硫醇形式。BES 没有使空气氧化的 2-KPCC 失活，其中氧化还原活性半胱氨酸对处于二硫化物形式。2-KPCC 的失活表现出饱和动力学，而 CoM 减慢了失活的速度。质谱分析表明 BES 灭活减少的 2-KPCC

  DOI：

  10.1074/jbc.m110.144410
• 作为产物：
  描述：

  (R)-2-hydroxypropyl-CoM(1-) 在 乙二胺四乙酸 、 recombinant 2-(R)-hydroxypropyl-coenzyme M dehydrogenase 、 β-烟酰胺腺嘌呤二核苷酸 作用下， 生成 2-oxopropyl-CoM(1-)
  参考文献：
  名称：

  辅酶 M 类似物 2-溴乙磺酸酯抑制脂肪族环氧化物羧化的机制。

  摘要：

  丙烯氧化形成的环氧丙烷的细菌代谢使用非典型辅酶辅酶 M（CoM，2-巯基乙磺酸盐）作为环氧化物开环的亲核试剂和中间体的载体，在三个过程中经过脱氢、还原裂解和羧化形成乙酰乙酸盐。 -步代谢途径。2-酮丙基-CoM 羧化酶/氧化还原酶 (2-KPCC)，该途径的末端酶，是二硫化物氧化还原酶家族中唯一已知的羧化酶成员。在目前的工作中，CoM 类似物 2-溴乙磺酸 (BES) 被证明是 2-KPCC 和羟丙基-CoM 脱氢酶的可逆抑制剂，但不是环氧烷烃：CoM 转移酶的可逆抑制剂。进一步的研究表明，BES 是二硫苏糖醇还原的 2-KPCC 的时间依赖性灭活剂，其中氧化还原活性半胱氨酸呈游离硫醇形式。BES 没有使空气氧化的 2-KPCC 失活，其中氧化还原活性半胱氨酸对处于二硫化物形式。2-KPCC 的失活表现出饱和动力学，而 CoM 减慢了失活的速度。质谱分析表明 BES 灭活减少的 2-KPCC

  DOI：

  10.1074/jbc.m110.144410

文献信息

• A role for coenzyme M (2-mercaptoethanesulfonic acid) in a bacterial pathway of aliphatic epoxide carboxylation
  作者：Jeffrey R. Allen、Daniel D. Clark、Jonathan G. Krum、Scott A. Ensign

  DOI：10.1073/pnas.96.15.8432

  日期：1999.7.20

  methyl group carrier and activator, has been identified as the thiol and central cofactor of aliphatic epoxide carboxylation in the Gram-negative bacterium Xanthobacter strain Py2. Component I catalyzed the addition of coenzyme M to epoxypropane to form a beta-hydroxythioether, 2-(2-hydroxypropylthio)ethanesulfonate. Components III and IV catalyzed the NAD(+)-dependent stereoselective dehydrogenation

  短链脂肪族烯烃的细菌代谢通过氧化成环氧烷烃然后羧化成β-酮酸而发生。环氧烷烃羧化需要四种酶（组分 I-IV）、NADPH、NAD(+) 和以前未识别的亲核硫醇。在目前的工作中，辅酶 M（2-巯基乙磺酸）是一种以前仅在产甲烷古细菌中发现的化合物，它作为甲基载体和活化剂，已被确定为革兰氏脂肪族环氧化物羧化的硫醇和中心辅助因子- 阴性细菌 Xanthobacter 菌株 Py2。组分I催化辅酶M与环氧丙烷加成形成β-羟基硫醚，2-(2-羟基丙硫基)乙磺酸盐。组分 III 和 IV 催化 2-(2-hydroxypropylthio)ethanesulfonate 的 R-和 S-对映体依赖于 NAD(+) 的立体选择性脱氢，形成 2-(2-ketopropylthio)ethanesulfonate。组分 II 催化 β-酮硫醚的 NADPH 依赖性裂解和羧化，形成乙酰乙酸和辅酶 M。这些发现表明辅酶
• Aliphatic Epoxide Carboxylation
  作者：Scott A. Ensign、Jeffrey R. Allen

  DOI：10.1146/annurev.biochem.72.121801.161820

  日期：2003.6

  three-step pathway resulting in net carboxylation to beta-ketoacids. This pathway uses the atypical cofactor coenzyme M (CoM; 2-mercaptoethanesulfonic acid) as the nucleophile for the epoxide ring opening and as the carrier of 2-hydroxyalkyl- and 2-ketoalkyl-CoM intermediates. Four enzymes are involved in epoxide carboxylation: a zinc-dependent alkyltransferase, two short-chain dehydrogenases with

  脂族环氧化物（环氧烷烃）是高反应性的亲电子分子，由单加氧酶催化的脂族烯烃环氧化形成。短链环氧烷烃的细菌代谢通过三步途径发生，导致净羧化为β-酮酸。该途径使用非典型辅因子辅酶M（CoM； 2-巯基乙磺酸）作为环氧化物开环的亲核试剂，并用作2-羟烷基-和2-酮烷基-CoM中间体的载体。环氧化物羧化涉及四种酶：锌依赖性烷基转移酶，对R-和S-1,2-环氧烷烃开环的手性产物具有特异性的两种短链脱氢酶和NADPH：-二硫化物氧化还原酶/羧化酶，其还原2-酮烷基-CoM共轭物的硫醚键并羧化所得的碳负离子。在这篇综述中，我们总结了环氧化物羧化酶的生化，机理和结构特征，并展示了这些酶与CoM如何协同工作以实现这种高度不同寻常的羧化反应。
• Structural Basis for CO₂ Fixation by a Novel Member of the Disulfide Oxidoreductase Family of Enzymes, 2-Ketopropyl-Coenzyme M Oxidoreductase/Carboxylase^,
  作者：Boguslaw Nocek、Se Bok Jang、Mi Suk Jeong、Daniel D. Clark、Scott A. Ensign、John W. Peters

  DOI：10.1021/bi026580p

  日期：2002.10.1

  The NADPH:2-ketopropyl-coenzyme M oxidoreductase/carboxylase (2-KPCC) is the terminal enzyme in a metabolic pathway that results in the conversion of propylene to the central metabolite acetoacetate in Xanthobacter autotrophicus Py2. This enzyme is an FAD-containing enzyme that is a member of the NADPH:disulfide oxidoreductase (DSOR) family of enzymes that include glutathione reductase, dihydrolipoamide dehydrogenase, trypanothione reductase, thioredoxin reductase, and mercuric reductase. In contrast to the prototypical reactions catalyzed by members of the DSOR family, the NADPH: 2-ketopropyl-coenzyme M oxidoreductase/carboxylase catalyzes the reductive cleavage of the thioether linkage of 2-ketopropyl-coenzyme M, and the subsequent carboxylation of the ketopropyl cleavage product, yielding the products acetoacetate and free coenzyme M. The structure of 2-KPCC reveals a unique active site in comparison to those of other members of the DSOR family of enzymes and demonstrates how the enzyme architecture has been adapted for the more sophisticated biochemical reaction. In addition, comparison of the structures in the native state and in the presence of bound substrate indicates the binding of the substrate 2-ketopropyl-coenzyme M induces a conformational change resulting in the collapse of the substrate access channel. The encapsulation of the substrate in this manner is reminiscent of the conformational changes observed in the well-characterized CO2-fixing enzyme ribulose 1,5-bisphosphate carboxylase/oxidase (Rubisco).
• Characterization of Five Catalytic Activities Associated with the NADPH:2-Ketopropyl-coenzyme M [2-(2-Ketopropylthio)ethanesulfonate] Oxidoreductase/Carboxylase of the <i>Xanthobacter</i> Strain Py2 Epoxide Carboxylase System
  作者：Daniel D. Clark、Jeffrey R. Allen、Scott A. Ensign

  DOI：10.1021/bi992282p

  日期：2000.2.1

  The bacterial metabolism of propylene proceeds by epoxidation to epoxypropane followed by carboxylation to acetoacetate. Epoxypropane carboxylation is a minimetabolic pathway that requires four enzymes, NADPH, NAD(+), and coenzyme M (CoM; 2-mercaptoethanesulfonate) and occurs with the overall reaction stoichiometry: epoxypropane + CO2 + NADPH + NAD(+) + CoM --> acetoacetate + H+ + NADP(+) + NADH + CoM. The terminal enzyme of the pathway is NADPH:2-ketopropyl-CoM [2-(2-keropropylthio)ethanesulfonate] oxidoreductase/carboxylase (2-KPCC), an FAD-containing enzyme that is a member of the NADPH:disulfide oxidoreductase family of enzymes and that catalyzes the reductive cleavage and carboxylation of 2-ketopropyl-CoM to form acetoacetate and CoM according to the reaction: 2-ketopropyl-CoM + NADPH + CO2 --> acetoacetate + NADP(+) + CoM. In the present work, 2-KPCC has been characterized with respect to the above reaction and four newly discovered partial reactions of relevance to the catalytic mechanism, and each of which requires the formation of a stabilized enolacetone intermediate. These four reactions are (1) NADPH-dependent cleavage and protonation of 2-ketopropyl-CoM to form NADP(+), CoM, and acetone, a reaction analogous to the physiological reaction but in which H+ is the electrophile; (2) NADP(+)-dependent synthesis of 2-ketopropyl-CoM from CoM and acetoacetate, the reverse of the physiologically important forward reaction; (3) acetoacetate decarboxylation to form acetone and CO2; and (4) acetoacetate/(CO2)-C-14 exchange to form C-14(1)-acetoacetate and CO2. Acetoacetate decarboxylation and (CO2)-C-14 exchange occurred independent of NADP(H) and CoM, demonstrating that these substrates are not central to the mechanism of enolate generation and stabilization. 2-KPCC did nor uncouple NADPH oxidation or NADP(+) reduction from the reactions involving cleavage or formation of 2-ketopropyl-CoM. N-Ethylmaleimide inactivated the reactions forming/using 2-ketopropyl-CoM but did not inactivate acetoacetate decarboxylation or (CO2)-C-14 exchange reactions. The biochemical characterization of 2-KPCC and the associated five catalytic activities has allowed the formulation of an unprecedented mechanism of substrate activation and carboxylation that involves NADPH oxidation, a redox active disulfide, thiol-mediated reductive cleavage of a C-S thioether bond, the formation of a CoM:cysteine mixed disulfide, and enolacetone stabilization.
• Mechanism of Inhibition of Aliphatic Epoxide Carboxylation by the Coenzyme M Analog 2-Bromoethanesulfonate
  作者：Jeffrey M. Boyd、Daniel D. Clark、Melissa A. Kofoed、Scott A. Ensign

  DOI：10.1074/jbc.m110.144410

  日期：2010.8

  The flavin thiol Cys(87) was not alkylated by BES under reducing conditions, and no amino acid residues were modified by BES in the oxidized enzyme. The UV-visible spectrum of BES-modifed 2-KPCC showed the characteristic charge transfer absorbance expected with alkylation at Cys(82). These results identify BES as a reactive CoM analog that specifically alkylates the interchange thiol that facilitates

  丙烯氧化形成的环氧丙烷的细菌代谢使用非典型辅酶辅酶 M（CoM，2-巯基乙磺酸盐）作为环氧化物开环的亲核试剂和中间体的载体，在三个过程中经过脱氢、还原裂解和羧化形成乙酰乙酸盐。 -步代谢途径。2-酮丙基-CoM 羧化酶/氧化还原酶 (2-KPCC)，该途径的末端酶，是二硫化物氧化还原酶家族中唯一已知的羧化酶成员。在目前的工作中，CoM 类似物 2-溴乙磺酸 (BES) 被证明是 2-KPCC 和羟丙基-CoM 脱氢酶的可逆抑制剂，但不是环氧烷烃：CoM 转移酶的可逆抑制剂。进一步的研究表明，BES 是二硫苏糖醇还原的 2-KPCC 的时间依赖性灭活剂，其中氧化还原活性半胱氨酸呈游离硫醇形式。BES 没有使空气氧化的 2-KPCC 失活，其中氧化还原活性半胱氨酸对处于二硫化物形式。2-KPCC 的失活表现出饱和动力学，而 CoM 减慢了失活的速度。质谱分析表明 BES 灭活减少的 2-KPCC