α-ketoglutaramate | 18507-11-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: α-ketoglutaramate
• 英文别名: 5-hydroxy-4,5-dioxopentanimidate
• CAS: 18507-11-4
• 化学式: C₅H₆NO₄
• 分子量: 144.107
• InChiKey: COJBGNAUUSNXHX-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  α-ketoglutaramate 在 recombinant human nitrilase-like protein 2 / ω-amidase 作用下， 反应 0.05h， 生成 2-氧代-戊二酸离子(2-)
  参考文献：
  名称：

  对催化活性位点和人类 Nit2/omega-酰胺酶活性的结构洞察：动力学分析和分子动力学模拟。

  摘要：

  人类腈水解酶样蛋白 2 (hNit2) 是一种推定的肿瘤抑制因子，最近被鉴定为 omega-酰胺酶。hNit2/omega-酰胺酶通过催化 α-酮戊二酸（谷氨酰胺的 α-酮类似物）和 α-酮琥珀酸（天冬酰胺的 α-酮类似物）的水解，分别产生 α-酮戊二酸和草酰乙酸，发挥重要的代谢作用。谷氨酰胺和 alpha-keto-gamma-methiolbutyrate 之间的转氨作用关闭了蛋氨酸补救途径。因此，hNit2/omega-酰胺酶将硫代谢与三羧酸循环联系起来。为了阐明 hNit2/omega-酰胺酶的催化特异性，我们对野生型酶及其突变体进行了分子动力学模拟，以研究酶-底物相互作用。计算结合自由能以表征促成底物特异性的因素。由这些计算得出的预测得到了动力学分析和突变研究的验证。hNit2/omega-酰胺酶的活性用α-酮戊二酸和琥珀酸作为底物测定。我们构建了三个催化三联体突变体（E43A、K112A

  DOI：

  10.1074/jbc.m111.259119
• 作为产物：
  描述：

  苯丙酮酸阴离子 、 L-谷氨酰胺 生成 α-ketoglutaramate 、 L-苯丙氨酸
  参考文献：
  名称：

  Structural Insight into the Inhibition of Human Kynurenine Aminotransferase I/Glutamine Transaminase K

  摘要：

  Human kynurenine aminotransferase I (hKAT I) catalyzes the formation of kynurenic acid, a neuroactive compound. Here, we report three high-resolution crystal structures (1.50-1.55 A) of hKAT I that are in complex with glycerol and each of two inhibitors of hKAT I: indole-3-acetic acid (IAC) and Tris. Because Tris is able to occupy the substrate binding position, we speculate that this may be the basis for hKAT I inhibition. Furthermore, the hKAT/IAC complex structure reveals that the binding moieties of the inhibitor are its indole ring and a carboxyl group. Six chemicals with both binding moieties were tested for their ability to inhibit hKAT I activity; 3-indolepropionic acid and DL-indole-3-lactic acid demonstrated the highest level of inhibition, and as they cannot be considered as substrates of the enzyme, these two inhibitors are promising candidates for future study. Perhaps even more significantly, we report the discovery of two different ligands located simultaneously in the hKAT I active center for the first time.

  DOI：

  10.1021/jm9000874

文献信息

• Identification of L-Glutamine: 2-Deoxy-scyllo-inosose Aminotransferase Required for the Biosynthesis of Butirosin in Bacillus circulans.
  作者：HIDEYUKI TAMEGAI、ERIKO NANGO、MIEKO KUWAHARA、HIDEKI YAMAMOTO、YASUMASA OTA、HISAKO KURIKI、TADASHI EGUCHI、KATSUMI KAKINUMA

  DOI：10.7164/antibiotics.55.707

  日期：——

  Using inverse PCR, two new genes (btrN and btrS) were identified upstream of the putative glycosyltransferase gene btrM in the butirosin-biosynthetic btr gene cluster of Bacillus circulans. The upstream gene btrS showed significant homology with stsC of Streptomyces griseus, which encodes L-glutamine: scyllo-inosose aminotransferase in the biosynthesis of streptomycin. The function of BtrS was further confirmed by heterologous expression in Escherichia coli and chemical identification of the conversion of 2-deoxy-scyllo-inosose into 2-deoxy-scyllo-inosamine. The identification of BtrS as L-glutamine: 2-deoxy-scyllo-inosose aminotransferase is the first report of the aminotransferase gene responsible for 2-deoxystreptamine biosynthesis.

  利用反向聚合酶链式反应（PCR）技术，在环状芽孢杆菌（Bacillus circulans）的丁香苷生物合成 btr 基因簇中的推定糖基转移酶基因 btrM 的上游发现了两个新基因（btrN 和 btrS）。上游基因 btrS 与灰葡萄孢链霉菌的 stsC 有显著的同源性，后者编码链霉素生物合成过程中的 L-谷氨酰胺：氨糖基转移酶。通过在大肠杆菌中的异源表达以及将 2-脱氧-酰基-肌糖苷转化为 2-脱氧-酰基-肌糖苷的化学鉴定，进一步证实了 BtrS 的功能。BtrS 被鉴定为 L-谷氨酰胺：2-deoxy-scyllo-inosose 转氨酶，这是首次报道负责 2-脱氧链霉胺生物合成的转氨酶基因。
• Biosynthesis of aminoglycoside antibiotics: cloning, expression and characterisation of an aminotransferase involved in the pathway to 2-deoxystreptamineElectronic supplementary information (ESI) available: LC-MS, TLC and ESI-Q-TOF MS. See http://www.rsc.org/suppdata/cc/b2/b209799k/
  作者：Fanglu Huang、Yanyan Li、Jinquan Yu、Jonathan B. Spencer

  DOI：10.1039/b209799k

  日期：2002.11.18

  Bacillus circulans has been cloned and expressed and shown to produce a protein which catalyses the transamination of 2-deoxy-scyllo-inosose to give 2-deoxy-scyllo-inosamine, an intermediate in the biosynthesis of 2-deoxystreptamine.

  已克隆并表达了来自圆形芽孢杆菌的基因btrR，并显示产生了一种蛋白质，该蛋白质催化2-脱氧-鞘氨醇的氨基转移，得到2-脱氧-鞘氨醇，其是2-脱氧链胺的生物合成的中间体。
• 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。
• Biosynthesis of 2-Deoxystreptamine by Three Crucial Enzymes in Streptomyces fradiae NBRC 12773
  作者：Fumitaka Kudo、Yasuhito Yamamoto、Kenichi Yokoyama、Tadashi Eguchi、Katsumi Kakinuma

  DOI：10.1038/ja.2005.104

  日期：2005.12

  NeoA, B, and C encoded in the neomycin biosynthetic gene cluster have been enzymatically confirmed to be responsible to the formation of 2-deoxystreptamine (DOS) in Streptomyces fradiae. NeoC was functionally characterized as 2-deoxy-scyllo-inosose synthase, which catalyzes the carbocycle formation from D-glucose-6-phosphate to 2-deoxy-scyllo-inosose. Further, NeoA appeared to catalyze the oxidation of 2-deoxy-scyllo-inosamine (DOIA) with NAD(P)+ forming 3-amino-2,3-dideoxy-scyllo-inosose (amino-DOI). Consequently, NeoA was characterized as 2-deoxy-scyllo-inosamine dehydrogenase. Finally, amino-DOI produced by NeoA from DOIA was transformed into DOS by NeoB. Since NeoB (Neo6) was also reported to be L-glutamine:2-deoxy-scyllo-inosose aminotransferase, all the enzymes in the DOS biosynthesis were characterized for the first time.

  经酶切证实，新霉素生物合成基因簇中的 NeoA、B 和 C 负责在弗氏链霉菌中形成 2-脱氧链霉胺（DOS）。NeoC 在功能上被表征为 2-脱氧-酰基-肌糖合成酶，它催化从 D-葡萄糖-6-磷酸到 2-脱氧-酰基-肌糖的碳环形成。此外，NeoA 似乎还能催化 2-脱氧-酰基-氨基（DOIA）与 NAD(P)+ 的氧化，形成 3-氨基-2,3-二脱氧-酰基-氨基糖（amino-DOI）。因此，NeoA 被定性为 2-脱氧-酰-氨基脱氢酶。最后，NeoA 从 DOIA 生成的氨基-DOI 被 NeoB 转化为 DOS。由于 NeoB（Neo6）也被报道为 L-谷氨酰胺：2-脱氧-丝氨酰-肌糖氨基转移酶，DOS 生物合成过程中的所有酶都首次被定性。
• The neomycin biosynthetic gene cluster of Streptomyces fradiae NCIMB 8233: characterisation of an aminotransferase involved in the formation of 2-deoxystreptamine
  作者：Fanglu Huang、Stephen F. Haydock、Tatiana Mironenko、Dieter Spiteller、Yanyan Li、Jonathan B. Spencer

  DOI：10.1039/b501199j

  日期：——

  cluster of the 2-deoxystreptamine (DOS)-containing aminoglycoside antibiotic neomycin has been cloned for the first time by screening of a cosmid library of Streptomyces fradiae NCIMB 8233. Sequence analysis has identified 21 putative open reading frames (ORFs) in the neomycin gene cluster (neo) with significant protein sequence similarity to gene products involved in the biosynthesis of other DOS-containing

  通过筛选链霉菌NCIMB 8233的粘粒文库，首次克隆了含2-脱氧链胺胺（DOS）的氨基糖苷类抗生素新霉素的生物合成基因簇。序列分析已鉴定出21个推定的开放阅读框（ORF）。新霉素基因簇（neo）与参与其他含DOS的氨基糖苷生物合成所涉及的基因产物具有显着的蛋白质序列相似性，这些丁醇包括丁硫醇（btr），庆大霉素（gnt），妥布霉素（tbm）和卡那霉素（kan）。位于neo基因簇5'末端的是先前鉴定的新霉素磷酸转移酶基因（apH）。通过将Neo簇与btr，gnt，tbm和kan簇进行比较，揭示了neo和btr簇独特的三个基因。这表明在抗生素生物合成过程中，这三个基因可能与核糖部分向DOS环的转移有关。neo-6基因的产物在此处的特征是L-谷氨酰胺：2-脱氧-鞘氨醇氨基转移酶，负责DOS生物合成中的第一次转氨反应，支持基因簇的分配。