[N'-[(4R)-4-amino-4-carboxybutyl]carbamimidoyl]azanium

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [N'-[(4R)-4-amino-4-carboxybutyl]carbamimidoyl]azanium
• 化学式: C6H15N4O2+
• 分子量: 175.21
• InChiKey: ODKSFYDXXFIFQN-SCSAIBSYSA-O

计算性质

• 辛醇/水分配系数(LogP)：
  -3.5
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  134
• 氢给体数：
  4
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  A 、 [N'-[(4R)-4-amino-4-carboxybutyl]carbamimidoyl]azanium 生成 AH₂ 、 Iminoarginine(1+)
  参考文献：
  名称：

  Arginine racemization by coupled catabolic and anabolic dehydrogenases

  摘要：

  -氨基酸存在于许多不同机体的专门组件中。从优势的-L-对映体的外消旋合成-D-氨基酸是由单个酶催化的。在这里，我们报告了一种新型的2组分氨基酸外消旋酶，用于-D-精氨酸代谢中的-L-反转，它存在于铜绿假单胞菌中。从DNA微阵列分析中，发现了潜在的DauBAR操纵子（用于D-精氨酸利用）的未知功能，它受D-精氨酸高度诱导。通过发现具有DauA或DauB损伤的菌株无法将D-精氨酸用作唯一的碳源，证明了Dau操纵子在D-精氨酸代谢中的重要性。有两条证据表明DauA和DauB需要进行精氨酸的D-到-L-外消旋。首先，通过DauA或DauB的损伤，L-精氨酸辅助生长被D-精氨酸废除。其次，D-精氨酸诱导亲本菌株PAO1中的L-精氨酸特异性基因，但不诱导其DauA或DauB突变体。这个假设通过纯化酶的活性测量得到了进一步的支持：DauA催化D-精氨酸的氧化脱氨作用，将其转化为2-酮基精氨酸和氨，而DauB能够在NADPH或NADH存在的情况下使用2-酮基精氨酸和氨作为底物，并将它们转化为L-精氨酸。因此，我们提出DauA和DauB是偶联的分解和合成脱氢酶，用于进行精氨酸的D-到-L-外消旋，这是通过L-精氨酸分解途径的D-精氨酸利用的先决条件。

  DOI：

  10.1073/pnas.0808269106
• 作为产物：
  描述：

  H-Arg-OH 生成 [N'-[(4R)-4-amino-4-carboxybutyl]carbamimidoyl]azanium
  参考文献：
  名称：

  假单胞菌假单胞菌的周质，吡ido醛-5'-磷酸依赖性氨基酸消旋酶。

  摘要：

  吡ido醛5'-磷酸（PLP）依赖性氨基酸消旋体几乎在每种细菌中都存在，但底物特异性可能有很大差异。我们在这里通过经典方法从大肠杆菌中分离了大假单胞菌的克隆的广泛底物特异性消旋酶ArgR。该消旋酶具有生化特性，除其他方面外，已证实其主要对赖氨酸，精氨酸和鸟氨酸具有活性，而对丙氨酸仅具有弱活性，而经过比较研究的同一生物的丙氨酸消旋酶仅对丙氨酸起作用。出乎意料的是，对ArgR的氨基末端进行测序揭示了蛋白质的加工过程，信号肽被切割掉了。随后的定位研究表明，taetrolens和E. 大肠杆菌ArgR活性几乎只存在于周质中，这一特征迄今为止对于任何氨基酸消旋酶都未知。制备了带有羧基末端His-tag的ArgR衍生物，这被证明甚至可以定位在周质中缺乏双精氨酸易位（Tat）途径的大肠杆菌突变体中。这些数据表明，ArgR被合成为前肽，并以与Tat无关的方式易位。因此，我们建议ArgR易位取决于Sec系统

  DOI：

  10.1007/s00253-009-1942-7

文献信息

• Insights on the Mechanism of Amine Oxidation Catalyzed by <scp>d</scp>-Arginine Dehydrogenase Through pH and Kinetic Isotope Effects
  作者：Hongling Yuan、Yao Xin、Donald Hamelberg、Giovanni Gadda

  DOI：10.1021/ja2082729

  日期：2011.11.23

  The mechanism of amine oxidation catalyzed by D-arginine dehydrogenase (DADH) has been investigated using steady-state and rapid reaction kinetics, with pH, substrate and solvent deuterium kinetic isotope effects (KIE) as mechanistic probes, and computational studies. Previous results showed that 85-90% of the flavin reduction reaction occurs in the mixing time of the stopped-flow spectrophotometer

  D-精氨酸脱氢酶 (DADH) 催化的胺氧化机制已经使用稳态和快速反应动力学进行了研究，pH、底物和溶剂氘动力学同位素效应 (KIE) 作为机制探针和计算研究。先前的结果表明，当精氨酸为底物时，85-90% 的黄素还原反应发生在停流分光光度计的混合时间，排除了机理研究。因此，具有较慢动力学的亮氨酸在这里被用作黄素还原底物。自由能计算和 K(d) 的 pH 值与优先结合底物的两性离子形式的酶一致。Michaelis 复合物的异构化，产生能够还原黄素的酶-底物复合物，由于 k(cat)/K(m) 对溶剂粘度的反双曲线依赖性而建立。胺去质子化触发氧化反应，底物 NH 和 CH 键以异步方式裂解，正如多氘 KIE 对黄素还原速率常数（k（红色））的暗示。9.6 的 pK(a) 表示促进非质子化形式的黄素还原的基团的电离。先前报道的 DADH 的亚氨基精氨酸和亚氨基组氨酸复合物的高分辨率晶体结构使我们能够提出
• A periplasmic, pyridoxal-5′-phosphate-dependent amino acid racemase in Pseudomonas taetrolens
  作者：Daisuke Matsui、Tadao Oikawa、Noriaki Arakawa、Shintaro Osumi、Frank Lausberg、Norma Stäbler、Roland Freudl、Lothar Eggeling

  DOI：10.1007/s00253-009-1942-7

  日期：2009.7

  The pyridoxal-5'-phosphate (PLP)-dependent amino acid racemases occur in almost every bacterium but may differ considerably with respect to substrate specificity. We here isolated the cloned broad substrate specificity racemase ArgR of Pseudomonas taetrolens from Escherichia coli by classical procedures. The racemase was biochemically characterized and amongst other aspects it was confirmed that it

  吡ido醛5'-磷酸（PLP）依赖性氨基酸消旋体几乎在每种细菌中都存在，但底物特异性可能有很大差异。我们在这里通过经典方法从大肠杆菌中分离了大假单胞菌的克隆的广泛底物特异性消旋酶ArgR。该消旋酶具有生化特性，除其他方面外，已证实其主要对赖氨酸，精氨酸和鸟氨酸具有活性，而对丙氨酸仅具有弱活性，而经过比较研究的同一生物的丙氨酸消旋酶仅对丙氨酸起作用。出乎意料的是，对ArgR的氨基末端进行测序揭示了蛋白质的加工过程，信号肽被切割掉了。随后的定位研究表明，taetrolens和E. 大肠杆菌ArgR活性几乎只存在于周质中，这一特征迄今为止对于任何氨基酸消旋酶都未知。制备了带有羧基末端His-tag的ArgR衍生物，这被证明甚至可以定位在周质中缺乏双精氨酸易位（Tat）途径的大肠杆菌突变体中。这些数据表明，ArgR被合成为前肽，并以与Tat无关的方式易位。因此，我们建议ArgR易位取决于Sec系统
• Regulation of the dauBAR operon and characterization of d-amino acid dehydrogenase DauA in arginine and lysine catabolism of Pseudomonas aeruginosa PAO1
  作者：Congran Li、Xiangyu Yao、Chung-Dar Lu

  DOI：10.1099/mic.0.033282-0

  日期：2010.1.1

  A unique d-to-l racemization of arginine by coupled arginine dehydrogenases DauA and DauB encoded by the dauBAR operon has been recently reported as a prerequisite for d-arginine utilization as the sole source of carbon and nitrogen through l-arginine catabolic pathways in P. aeruginosa. In this study, enzymic properties of the catabolic FAD-dependent d-amino acid dehydrogenase DauA and the physiological functions of the dauBAR operon were further characterized with other d-amino acids. These results establish DauA as a d-amino acid dehydrogenase of broad substrate specificity, with d-Arg and d-Lys as the two most effective substrates, based on the kinetic parameters. In addition, expression of dauBAR is specifically induced by exogenous d-Arg and d-Lys, and mutations in the dauBAR operon affect utilization of these two amino acids alone. The function of DauR as a repressor in the control of the dauBAR operon was demonstrated by dauB promoter activity measurements in vivo and mobility shift assays with purified His-tagged protein in vitro. The potential effect of 2-ketoarginine (2-KA) derived from d-Arg deamination by DauA as a signal molecule in dauBAR induction was first revealed by mutation analysis and further supported by its in vitro effect on alleviation of DauR–DNA interactions. Through sequence analysis, putative DauR operators were identified and confirmed by mutation analysis. Induction of the dauBAR operon to the maximal level was found to require the l-arginine-responsive regulator ArgR, as supported by the loss of inductive effect by l-Arg on dauBAR expression in the argR mutant and binding of purified ArgR to the dauB regulatory region in vitro. In summary, this study establishes that optimal induction of the dauBAR operon requires relief of DauR repression by 2-KA and activation of ArgR by l-Arg as a result of d-Arg racemization by the encoded DauA and DauB.

  最近的一项研究报道了由耦合的精氨酸脱氢酶DauA和DauB编码的dauBAR操纵子所引起的独特的D-精氨酸到L-精氨酸的旋光异构化，作为在P. aeruginosa中通过L-精氨酸分解途径利用D-精氨酸作为唯一的碳和氮源的先决条件。在这项研究中，进一步表征了这个分解FAD依赖性的D-氨基酸脱氢酶DauA的酶学性质和dauBAR操纵子的生理功能。这些结果确定了DauA作为广泛底物特异性的D-氨基酸脱氢酶，基于动力学参数，D-精氨酸和D-赖氨酸是最有效的两种底物。此外，dauBAR的表达受外源D-精氨酸和D-赖氨酸的特异性诱导，dauBAR操纵子的突变影响了这两种氨基酸的利用。通过in vivo的dauB启动子活性测量和in vitro的纯化His-标记蛋白的迁移移位实验，证明了DauR作为抑制子在dauBAR操纵子的控制中的功能。通过突变分析首次揭示了DauA脱氨基反应产生的2-酮基精氨酸（2-KA）作为信号分子在dauBAR诱导中的潜在作用，并通过其在in vitro中缓解DauR-DNA相互作用的效应予以进一步支持。通过序列分析，鉴定了推测的DauR操作员，并通过突变分析进行了确认。总之，这项研究确定了dauBAR操纵子的最佳诱导需要通过2-KA缓解DauR的抑制作用并通过由编码的DauA和DauB引起的D-精氨酸旋光异构化激活ArgR。
• D-Arginase of Arthrobacter sp. KUJ 8602: Characterization and Its Identity with Zn2+-Guanidinobutyrase
  作者：N. Arakawa

  DOI：10.1093/jb/mvg016

  日期：2003.1.1

  d-Arginase activity was found in the cells of an isolate, Arthrobacter sp. KUJ 8602, grown in the l-arginine medium, and the enzyme was purified and characterized. Its molecular weight was estimated to be about 232,000 by gel filtration, and that of the subunit was approximately 40,000 by SDS-PAGE, suggesting that the enzyme is a homohexamer. The enzyme acted on not only d-arginine but also 4-guanidinobutyrate, 3-guanidinopropionate and even l-arginine. The Vmax/Km values for 4-guanidinobutyrate and d-arginine were determined to be 87 and 0.81 µmol/min/mg/mM, respectively. Accordingly, the enzyme is regarded as a kind of guanidinobutyrase [EC 3.5.3.7]. The pH optima for 4-guanidinobutyrate and d-arginine were 9.0 and 9.5, respectively. The enzyme was inhibited competitively by 5-aminovalerate, and thiol carboxylates such as mercaptoacetate served as strong mixed-type inhibitors. The enzyme contained about 1 g-atom of firmly bound Zn2+ per mol of subunit, and removal of the metal ions by incubation with 1,10-phenanthroline resulted in loss of activity. The inactivated enzyme was reactivated markedly by incubation with either Zn2+ or Co2+, and slightly by incubation with Mn2+. The nucleotide sequence of enzyme contains an open reading frame that encodes a polypeptide of 353 amino acid residues (Mr: 37,933). The predicted amino acid sequence contains sequences involved in the binding of metal ions and the guanidino group of the substrate, which show a high homology with corresponding sequences of Mn2+-dependent amidinohydrolases such as agmatinase from Escherichia coli and l-arginase from rat liver, though the homology of their entire sequences is relatively low (24–43%).

  not yet确定。
• Arginine racemization by coupled catabolic and anabolic dehydrogenases
  作者：Congran Li、Chung-Dar Lu

  DOI：10.1073/pnas.0808269106

  日期：2009.1.20

  d -Amino acids exist in living organisms as specialized components of many different machineries. Biosynthesis of d -amino acids from racemization of predominant l -enantiomers is catalyzed by a single enzyme. Here, we report the finding of a novel 2-component amino acid racemase for d -to- l inversion in d -arginine metabolism of Pseudomonas aeruginosa . From DNA microarray analysis, the putative dauBAR operon (for d -arginine utilization) of unknown functions was found to be highly induced by d -arginine. The importance of the dau operon in d -arginine metabolism was demonstrated by the findings that strains with a lesion at dauA or dauB failed to use d -arginine as sole carbon source. Two lines of evidence suggest that DauA and DauB are required for d -to- l racemization of arginine. First, growth complementation of an l -arginine auxotroph by d -arginine was abolished by a lesion at dauA or dauB . Second, d -arginine induced l -arginine-specific genes in the parental strain PAO1 but not in its dauA or dauB mutants. This hypothesis was further supported by activity measurements of the purified enzymes: DauA catalyzes oxidative deamination of d -arginine into 2-ketoarginine and ammonia, and DauB is able to use 2-ketoarginine and ammonia as substrates and convert them into l -arginine in the presence of NADPH or NADH. Thus, we propose that DauA and DauB are coupled catabolic and anabolic dehydrogenases to perform d -to- l racemization of arginine, which serves as prerequisite of d -arginine utilization through l -arginine catabolic pathways.

  -氨基酸存在于许多不同机体的专门组件中。从优势的-L-对映体的外消旋合成-D-氨基酸是由单个酶催化的。在这里，我们报告了一种新型的2组分氨基酸外消旋酶，用于-D-精氨酸代谢中的-L-反转，它存在于铜绿假单胞菌中。从DNA微阵列分析中，发现了潜在的DauBAR操纵子（用于D-精氨酸利用）的未知功能，它受D-精氨酸高度诱导。通过发现具有DauA或DauB损伤的菌株无法将D-精氨酸用作唯一的碳源，证明了Dau操纵子在D-精氨酸代谢中的重要性。有两条证据表明DauA和DauB需要进行精氨酸的D-到-L-外消旋。首先，通过DauA或DauB的损伤，L-精氨酸辅助生长被D-精氨酸废除。其次，D-精氨酸诱导亲本菌株PAO1中的L-精氨酸特异性基因，但不诱导其DauA或DauB突变体。这个假设通过纯化酶的活性测量得到了进一步的支持：DauA催化D-精氨酸的氧化脱氨作用，将其转化为2-酮基精氨酸和氨，而DauB能够在NADPH或NADH存在的情况下使用2-酮基精氨酸和氨作为底物，并将它们转化为L-精氨酸。因此，我们提出DauA和DauB是偶联的分解和合成脱氢酶，用于进行精氨酸的D-到-L-外消旋，这是通过L-精氨酸分解途径的D-精氨酸利用的先决条件。