α-keto-γ-methylthio-butyrate | 88153-97-3

• 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: α-keto-γ-methylthio-butyrate
• 英文别名: 4-methylthio-2-oxobutanoate；ketomethylthiobutyrate；4-methylsulfanyl-2-oxobutanoate
• CAS: 88153-97-3
• 化学式: C₅H₇O₃S
• 分子量: 147.175
• InChiKey: SXFSQZDSUWACKX-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  9
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  82.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  α-keto-γ-methylthio-butyrate 在 L-谷氨酸 、 磷酸吡哆醛 作用下， 以 水 为溶剂， 反应 12.0h， 以58%的产率得到L-蛋氨酸
  参考文献：
  名称：

  Application of E. Coli aspartate transaminase to amino acid synthesis

  摘要：

  DOI：

  10.1016/s0040-4039(00)96374-3
• 作为产物：
  描述：

  2-氧代-戊二酸离子(2-) 、 L-蛋氨酸 生成 α-keto-γ-methylthio-butyrate 、 2-氨基戊二酸酯
  参考文献：
  名称：

  Mavrides C.; Orr W., J Biol Chem, 1975, 0021-9258, 4128-33

  摘要：

  DOI：

文献信息

• Snake Venom L-Amino Acid Oxidases: Trends in Pharmacology and Biochemistry
  作者：Luiz Fernando M. Izidoro、Juliana C. Sobrinho、Mirian M. Mendes、Tássia R. Costa、Amy N. Grabner、Veridiana M. Rodrigues、Saulo L. da Silva、Fernando B. Zanchi、Juliana P. Zuliani、Carla F. C. Fernandes、Leonardo A. Calderon、Rodrigo G. Stábeli、Andreimar M. Soares

  DOI：10.1155/2014/196754

  日期：——

  L-amino acid oxidases are enzymes found in several organisms, including venoms of snakes, where they contribute to the toxicity of ophidian envenomation. Their toxicity is primarily due to enzymatic activity, but other mechanisms have been proposed recently which require further investigation. L-amino acid oxidases exert biological and pharmacological effects, including actions on platelet aggregation and the induction of apoptosis, hemorrhage, and cytotoxicity. These proteins present a high biotechnological potential for the development of antimicrobial, antitumor, and antiprotozoan agents. This review provides an overview of the biochemical properties and pharmacological effects of snake venom L-amino acid oxidases, their structure/activity relationship, and supposed mechanisms of action described so far.

  L-氨基酸氧化酶是一种酶，存在于多种生物体中，包括蛇毒中，其中它们对蛇毒的毒性起着贡献。它们的毒性主要是由于酶活性，但最近提出了其他机制，需要进一步研究。L-氨基酸氧化酶对血小板聚集和诱导凋亡、出血和细胞毒性等具有生物学和药理学作用。这些蛋白质具有高度的生物技术潜力，可用于开发抗微生物、抗肿瘤和抗原虫药物。本综述概述了蛇毒L-氨基酸氧化酶的生化特性和药理学效应，它们的结构/活性关系以及迄今为止所描述的假定作用机制。
• Substrate specificity and structure of human aminoadipate aminotransferase/kynurenine aminotransferase II
  作者：Qian Han、Tao Cai、Danilo A. Tagle、Howard Robinson、Jianyong Li

  DOI：10.1042/bsr20080085

  日期：2008.8.1

  KAT (kynurenine aminotransferase) II is a primary enzyme in the brain for catalysing the transamination of kynurenine to KYNA (kynurenic acid). KYNA is the only known endogenous antagonist of the N-methyl-D-aspartate receptor. The enzyme also catalyses the transamination of aminoadipate to α-oxoadipate; therefore it was initially named AADAT (aminoadipate aminotransferase). As an endotoxin, aminoadipate influences various elements of glutamatergic neurotransmission and kills primary astrocytes in the brain. A number of studies dealing with the biochemical and functional characteristics of this enzyme exist in the literature, but a systematic assessment of KAT II addressing its substrate profile and kinetic properties has not been performed. The present study examines the biochemical and structural characterization of a human KAT II/AADAT. Substrate screening of human KAT II revealed that the enzyme has a very broad substrate specificity, is capable of catalysing the transamination of 16 out of 24 tested amino acids and could utilize all 16 tested α-oxo acids as amino-group acceptors. Kinetic analysis of human KAT II demonstrated its catalytic efficiency for individual amino-group donors and acceptors, providing information as to its preferred substrate affinity. Structural analysis of the human KAT II complex with α-oxoglutaric acid revealed a conformational change of an N-terminal fraction, residues 15–33, that is able to adapt to different substrate sizes, which provides a structural basis for its broad substrate specificity.

  KAT（犬尿氨酸氨基转移酶）Ⅱ是大脑中催化犬尿氨酸转化为 KYNA（犬尿酸）的主要酶。KYNA 是唯一已知的 N-甲基-D-天冬氨酸受体内源性拮抗剂。这种酶还能催化氨基己二酸向α-氧代己二酸的转化，因此最初被命名为 AADAT（氨基己二酸氨基转移酶）。作为一种内毒素，氨基己二酸盐会影响谷氨酸能神经传递的各种因素，并杀死大脑中的原发性星形胶质细胞。文献中有许多关于这种酶的生物化学和功能特性的研究，但尚未对 KAT II 的底物概况和动力学特性进行系统评估。本研究探讨了人 KAT II/AADAT 的生化和结构特征。人 KAT II 的底物筛选显示，该酶具有非常广泛的底物特异性，能够催化 24 种测试氨基酸中 16 种氨基酸的转氨基反应，并能利用所有 16 种测试的 α-氧代酸作为氨基基团接受体。对人类 KAT II 的动力学分析表明了它对单个氨基基团供体和受体的催化效率，从而提供了有关其首选底物亲和性的信息。对人 KAT II 与 α-oxoglutaric acid 复合物的结构分析表明，其 N 端部分残基 15-33 发生了构象变化，能够适应不同大小的底物，这为其广泛的底物特异性提供了结构基础。
• Biosynthesis of ethylene. 4-Methylmercapto-2-oxobutyric acid, an intermediate in the formation from methionine
  作者：L. W. Mapson、J. F. March、D. A. Wardale

  DOI：10.1042/bj1150653

  日期：1969.12.1

  The enzyme responsible for the conversion of methionine into a precursor of ethylene in cauliflower florets is a transaminase. The formation of 4-methyl-mercapto-2-oxobutyric acid by this enzyme has been shown. The oxo acid stimulates the synthesis of ethylene when added to floret tissue, and tracer experiments have shown that 14C is incorporated into ethylene from the labelled oxo acid. The evidence is consistent with the view that the oxo acid is an intermediate in the formation of ethylene from methionine.

  花椰菜花蕾中将蛋氨酸转化为乙烯前体的酶是转氨酶。已经证明该酶可形成4-甲基硫代-2-酮丁酸。当将该酮酸加入花蕾组织中时，酮酸会刺激乙烯的合成。示踪实验表明，标记的14C从标记的酮酸中被并入了乙烯中。这些证据与酮酸是从蛋氨酸中形成乙烯的中间体的观点一致。
• Characterization of a thiamin diphosphate-dependent phenylpyruvate decarboxylase from Saccharomyces cerevisiae
  作者：Malea M. Kneen、Razvan Stan、Alejandra Yep、Ryan P. Tyler、Choedchai Saehuan、Michael J. McLeish

  DOI：10.1111/j.1742-4658.2011.08103.x

  日期：2011.6

  phenylalanine, tryptophan and possibly also tyrosine catabolism. However, its substrate spectrum suggests that it is unlikely to play any significant role in the catabolism of the branched-chain amino acids or of methionine. A homology model was used to identify residues likely to be involved in substrate specificity. Site-directed mutagenesis on those residues confirmed previous studies indicating that mutation

  来自酿酒酵母的ARO10基因的产物最初被鉴定为具有广泛底物特异性的硫胺素二磷酸依赖性苯丙酮酸脱羧酶。有人提出该酶可能是芳香族和支链氨基酸以及蛋氨酸的分解代谢的原因。在本研究中，我们报告了ARO10基因产物在大肠杆菌中的过表达和该酶的首次详细体外表征。该酶被证明是一种有效的芳香族2-酮酸脱羧酶，与其在苯丙氨酸，色氨酸以及酪氨酸分解代谢中起主要的体内作用相一致。但是，其底物光谱表明，它不太可能在支链氨基酸或蛋氨酸的分解代谢中发挥重要作用。同源性模型用于鉴定可能与底物特异性有关的残基。这些残基的定点诱变证实了先前的研究，表明单个残基的突变不太可能导致芳香族立即转化为脂肪族2-酮酸脱羧酶。另外，将该酶与来自巴西固氮螺菌的苯基丙酮酸脱羧酶和来自阴沟肠杆菌的吲哚丙酮酸脱羧酶进行了比较。我们表明，这两种丙酮丙酮酸脱羧酶的性质在某些方面相似，而在另一些方面则完全不同，并且两者的性质都与吲哚丙酮酸脱羧酶的性质不同。最后，
• Tyrosine Aminotransferase Catalyzes the Final Step of Methionine Recycling in <i>Klebsiella pneumoniae</i>
  作者：Jacqueline Heilbronn、Judith Wilson、Bradley J. Berger

  DOI：10.1128/jb.181.6.1739-1747.1999

  日期：1999.3.15

  tyrosine with alpha-ketoglutarate and tyrosine with oxaloacetate normally associated with tyrosine aminotransferases. The aminotransferase was inhibited by the aminooxy compounds canaline and carboxymethoxylamine but not by substrate analogues, such as nitrotyrosine or nitrophenylalanine.

  已从肺炎克雷伯菌中纯化并表征了一种氨基转移酶，该酶催化甲硫氨酸从甲硫腺苷再循环的最后一步，即 α-酮基硫代丁酸转化为甲硫氨酸。该酶被发现是 45-kDa 亚基的同源二聚体，它主要使用芳香族氨基酸和谷氨酸作为氨基供体催化甲硫氨酸的形成。组氨酸、亮氨酸、天冬酰胺和精氨酸也是功能性氨基供体，但程度较小。测定该酶的 N 端氨基酸序列，发现与大肠杆菌和鼠伤寒沙门氏菌酪氨酸氨基转移酶（tyrB 基因产物）的 N 端序列几乎相同。酪氨酸氨基转移酶的结构基因从肺炎克雷伯菌中克隆并在大肠杆菌中表达。推导的氨基酸序列分别与大肠杆菌、鼠伤寒沙门氏菌、反硝化副球菌和苜蓿根瘤菌的酪氨酸氨基转移酶具有 83%、80%、38% 和 34% 的同一性，但与任何特征性真核生物的同一性不到 13%酪氨酸氨基转移酶。关键不变残基周围的结构基序将肺炎克雷伯菌酶置于转氨酶的 Ia 亚家族中。氨基转移酶的动力学分析表明，芳香族氨基酸