(S)-ureidoglycine | 136774-67-9

• 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: (S)-ureidoglycine
• 英文别名: (S)-2-ureidoglycine；(2S)-2-amino-2-(carbamoylamino)acetic acid
• CAS: 136774-67-9
• 化学式: C₃H₇N₃O₃
• 分子量: 133.107
• InChiKey: VTFWFHCECSOPSX-SFOWXEAESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.5
• 重原子数：
  9
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  118
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-ureidoglycine 在 (S)-ureidoglycine aminohydrolase from Arabidopsis thaliana 作用下， 生成 (2S)-(氨基甲酰氨基)(羟基)乙酸
  参考文献：
  名称：

  Structural and Functional Insights into (S)-Ureidoglycine Aminohydrolase, Key Enzyme of Purine Catabolism in Arabidopsis thaliana

  摘要：

  The ureide pathway has recently been identified as the metabolic route of purine catabolism in plants and some bacteria. In this pathway, uric acid, which is a major product of the early stage of purine catabolism, is degraded into glyoxylate and ammonia via stepwise reactions of seven different enzymes. Therefore, the pathway has a possible physiological role in mobilization of purine ring nitrogen for further assimilation. (S)-Ureidoglycine aminohydrolase enzyme converts (S)-ureidoglycine into (S)-ureidoglycolate and ammonia, providing the final substrate to the pathway. Here, we report a structural and functional analysis of this enzyme from Arabidopsis thaliana (AtUGlyAH). The crystal structure of AtUGlyAH in the ligand-free form shows a monomer structure in the bicupin fold of the beta-barrel and an octameric functional unit as well as a Mn2+ ion binding site. The structure of AtUGlyAH in complex with (S)-ureidoglycine revealed that the Mn2+ ion acts as a molecular anchor to bind (S)-ureidoglycine, and its binding mode dictates the enantioselectivity of the reaction. Further kinetic analysis characterized the functional roles of the active site residues, including the Mn2+ ion binding site and residues in the vicinity of (S)-ureidoglycine. These analyses provide molecular insights into the structure of the enzyme and its possible catalytic mechanism.

  DOI：

  10.1074/jbc.m111.331819
• 作为产物：
  描述：

  Allantoate 、 氢(+1)阳离子 、 水 生成 (S)-ureidoglycine 、 二氧化碳 、 铵
  参考文献：
  名称：

  Structural Analysis of a Ternary Complex of Allantoate Amidohydrolase from Escherichia coli Reveals its Mechanics

  摘要：

  Purine metabolism plays a major role in regulating the availability of purine nucleotides destined for nucleic acid synthesis. Allantoate amidohydrolase catalyzes the conversion of allantoate to (S)-ureidoglycolate, one of the crucial alternate steps in purine metabolism. The crystal structure of a ternary complex of allantoate amidohydrolase with its substrate allantoate and an allosteric effector, a sulfate ion, from Escherichia coli was determined to understand better the catalytic mechanism and substrate specificity. The 2.25 A resolution X-ray structure reveals an alpha/beta scaffold akin to zinc exopeptidases of the peptidase M20 family and lacks the (beta/alpha)(8)-barrel fold characteristic of the amidohydrolases. Arrangement of the substrate and the two co-catalytic zinc ions at the active site governs catalytic specificity for hydrolysis of N-carbamyl versus the peptide bond in exopeptidases. In its crystalline form, allantoate amidohydrolase adopts a relatively open conformation. However, structural analysis reveals the possibility of a significant movement of domains via rotation about two hinge regions upon allosteric effector and substrate binding resulting in a closed catalytically competent conformation by bringing the substrate allantoate closer to co-catalytic zinc ions. Two cis-prolyl peptide bonds found on either side of the dimerization domain in close proximity to the substrate and ligand-binding sites may be involved in protein folding and in preserving the integrity of the catalytic site.

  DOI：

  10.1016/j.jmb.2007.02.028

文献信息

• Functional Analysis of 14 Genes That Constitute the Purine Catabolic Pathway in <i>Bacillus subtilis</i> and Evidence for a Novel Regulon Controlled by the PucR Transcription Activator
  作者：Anna C. Schultz、Per Nygaard、Hans H. Saxild

  DOI：10.1128/jb.183.11.3293-3302.2001

  日期：2001.6

  The soil bacterium Bacillus subtilis has developed a highly controlled system for the utilization of a diverse array of low-molecular-weight compounds as a nitrogen source when the preferred nitrogen sources, e.g., glutamate plus ammonia, are exhausted. We have identified such a system for the utilization of purines as nitrogen source in B. subtilis . Based on growth studies of strains with knockout mutations in genes, complemented with enzyme analysis, we could ascribe functions to 14 genes encoding enzymes or proteins of the purine degradation pathway. A functional xanthine dehydrogenase requires expression of five genes ( pucA, pucB, pucC, pucD , and pucE ). Uricase activity is encoded by the pucL and pucM genes, and a uric acid transport system is encoded by pucJ and pucK . Allantoinase is encoded by the pucH gene, and allantoin permease is encoded by the pucI gene. Allantoate amidohydrolase is encoded by pucF . In a pucR mutant, the level of expression was low for all genes tested, indicating that PucR is a positive regulator of puc gene expression. All 14 genes except pucI are located in a gene cluster at 284 to 285° on the chromosome and are contained in six transcription units, which are expressed when cells are grown with glutamate as the nitrogen source (limiting conditions), but not when grown on glutamate plus ammonia (excess conditions). Our data suggest that the 14 genes and the gde gene, encoding guanine deaminase, constitute a regulon controlled by the pucR gene product. Allantoic acid, allantoin, and uric acid were all found to function as effector molecules for PucR-dependent regulation of puc gene expression. When cells were grown in the presence of glutamate plus allantoin, a 3- to 10-fold increase in expression was seen for most of the genes. However, expression of the pucABCDE unit was decreased 16-fold, while expression of pucR was decreased 4-fold in the presence of allantoin. We have identified genes of the purine degradation pathway in B. subtilis and showed that their expression is subject to both general nitrogen catabolite control and pathway-specific control.

  摘要 土壤细菌 枯草芽孢杆菌 已开发出一种高度可控的系统，可在首选氮源（如谷氨酸和氨氮）耗尽时利用多种低分子量化合物作为氮源。我们已经在枯草芽孢杆菌中发现了这种利用嘌呤作为氮源的系统。 枯草芽孢杆菌 .根据对基因敲除突变菌株的生长研究，并辅以酶分析，我们可以为 14 个编码嘌呤降解途径的酶或蛋白质的基因赋予功能。一个功能性黄嘌呤脱氢酶需要五个基因的表达（pucA、pucB、pucC、pucB、pucC、pucC、pucC）。 pucA、pucB、pucC、pucD 和 pucE ).尿酸酶活性由 pucL 和 pucM 基因编码尿酸酶活性，尿酸转运系统由 和 和 pucK .尿囊素酶由 pucH 基因编码，尿囊素渗透酶由 pucI 基因编码。尿囊素酰胺水解酶由 pucF .在 突变体中 突变体中，所有测试基因的表达水平都很低，这表明 PucR 是 puc 基因的表达。除 pucI 以外的 14 个基因都位于染色体 284 至 285°的基因簇中，并包含在六个转录单元中，当细胞以谷氨酸为氮源生长时（限制条件），这些基因会表达，但当细胞以谷氨酸加氨生长时（过量条件），这些基因不会表达。我们的数据表明，这 14 个基因和 gde 基因（编码鸟嘌呤脱氨酶）构成了一个由 pucR 基因产物控制的调控子。研究发现尿囊酸、尿囊素和尿酸都是 PucR 依赖性调控的效应分子。 puc 基因表达的效应分子。当细胞在谷氨酸和尿囊素的作用下生长时，大多数基因的表达量会增加 3 到 10 倍。然而 pucABCDE 单元的表达量减少了 16 倍，而 pucR 的表达则下降了 4 倍。我们已经确定了枯草芽孢杆菌中嘌呤降解途径的基因。 嘌呤降解途径的基因 并发现它们的表达既受一般氮代谢物的控制，也受特定途径的控制。
• An aminotransferase branch point connects purine catabolism to amino acid recycling
  作者：Ileana Ramazzina、Roberto Costa、Laura Cendron、Rodolfo Berni、Alessio Peracchi、Giuseppe Zanotti、Riccardo Percudani

  DOI：10.1038/nchembio.445

  日期：2010.11

  Purine catabolism is typically thought to yield metabolic waste material. However, bioinformatics analysis, coupled with structural and biochemical investigations, now demonstrates that the central carbons of the purine ring can be recycled into glycine in B. subtilis and other bacteria. Although amino acids are known precursors of purines, a pathway for the direct recycling of amino acids from purines has never been described at the molecular level. We provide NMR and crystallographic evidence that the PucG protein from Bacillus subtilis catalyzes the transamination between an unstable intermediate ((S)-ureidoglycine) and the end product of purine catabolism (glyoxylate) to yield oxalurate and glycine. This activity enables soil and gut bacteria to use the animal purine waste as a source of carbon and nitrogen. The reaction catalyzed by (S)-ureidoglycine–glyoxylate aminotransferase (UGXT) illustrates a transamination sequence in which the same substrate provides both the amino group donor and, via its spontaneous decay, the amino group acceptor. Structural comparison and mutational analysis suggest a molecular rationale for the functional divergence between UGXT and peroxisomal alanine-glyoxylate aminotransferase, a fundamental enzyme for glyoxylate detoxification in humans.

  嘌呤分解代谢通常被认为会产生代谢废物。然而，生物信息学分析以及结构和生物化学研究现在证明，在枯草杆菌和其他细菌中，嘌呤环的中心碳可被回收为甘氨酸。 虽然氨基酸是已知的嘌呤前体，但从嘌呤直接回收氨基酸的途径从未在分子水平上被描述过。我们提供的核磁共振和晶体学证据表明，枯草芽孢杆菌的 PucG 蛋白催化了不稳定中间体（(S)-脲基甘氨酸）与嘌呤分解代谢最终产物（乙醛酸）之间的转氨作用，从而产生草酸和甘氨酸。这种活性使土壤和肠道细菌能够利用动物嘌呤废物作为碳源和氮源。(S)-脲基甘氨酸乙醛酸氨基转移酶（UGXT）催化的反应说明了一种转氨酶序列，其中相同的底物既提供了氨基供体，又通过自发衰变提供了氨基受体。结构比较和突变分析表明了 UGXT 与过氧物酶体丙氨酸-乙醛酸氨基转移酶（人类乙醛酸解毒的基本酶）之间功能差异的分子原理。
• Identifying reaction modules in metabolic pathways: bioinformatic deduction and experimental validation of a new putative route in purine catabolism
  作者：Matthieu Barba、Raphaël Dutoit、Christianne Legrain、Bernard Labedan

  DOI：10.1186/1752-0509-7-99

  日期：2013.12

  Enzymes belonging to mechanistically diverse superfamilies often display similar catalytic mechanisms. We previously observed such an association in the case of the cyclic amidohydrolase superfamily whose members play a role in related steps of purine and pyrimidine metabolic pathways. To establish a possible link between enzyme homology and chemical similarity, we investigated further the neighbouring steps in the respective pathways.

  We identified that successive reactions of the purine and pyrimidine pathways display similar chemistry. These mechanistically-related reactions are often catalyzed by homologous enzymes. Detection of series of similar catalysis made by succeeding enzyme families suggested some modularity in the architecture of the central metabolism. Accordingly, we introduce the concept of a reaction module to define at least two successive steps catalyzed by homologous enzymes in pathways alignable by similar chemical reactions. Applying such a concept allowed us to propose new function for misannotated paralogues. In particular, we discovered a putative ureidoglycine carbamoyltransferase (UGTCase) activity. Finally, we present experimental data supporting the conclusion that this UGTCase is likely to be involved in a new route in purine catabolism.

  Using the reaction module concept should be of great value. It will help us to trace how the primordial promiscuous enzymes were assembled progressively in functional modules, as the present pathways diverged from ancestral pathways to give birth to the present-day mechanistically diversified superfamilies. In addition, the concept allows the determination of the actual function of misannotated proteins.

  机械多样的酶超家族中的酶通常显示出相似的催化机制。我们之前在环状酰胺水解酶超家族中观察到了这样的关联，其成员在嘌呤和嘧啶代谢途径的相关步骤中发挥作用。为了建立酶同源和化学相似性之间的可能联系，我们进一步研究了各自途径中的相邻步骤。

  我们确定了嘌呤和嘧啶途径的连续反应显示出相似的化学反应。这些机制相关的反应通常由同源酶催化。检测到由连续酶家族进行的一系列相似催化反应，表明中心代谢的结构具有一定的模块化。因此，我们引入了反应模块的概念，以定义由类似化学反应可对齐的途径中由同源酶催化的至少两个连续步骤。应用这样的概念使我们能够为错注释的同源基因提出新的功能。特别是，我们发现了一种可能的尿素甘氨酸羧酰转移酶（UGTCase）活性。最后，我们提供实验数据支持结论，即这种UGTCase可能参与嘌呤降解中的新途径。

  使用反应模块概念应该具有很大的价值。它将帮助我们追踪原始的杂合酶如何逐步组装成功能模块，随着现有途径从祖先途径分化出来，产生了现代机械多样的超家族。此外，该概念允许确定错注释蛋白质的实际功能。

• Chemical Basis of Nitrogen Recovery through the Ureide Pathway: Formation and Hydrolysis of <i>S</i>-Ureidoglycine in Plants and Bacteria
  作者：Fabio Serventi、Ileana Ramazzina、Ilaria Lamberto、Vincenzo Puggioni、Rita Gatti、Riccardo Percudani

  DOI：10.1021/cb900248n

  日期：2010.2.19

  White some organisms, including humans, eliminate oxidized purines to get rid of excess nitrogen, for many others the recovery of the purine ring nitrogen is vital. In the so-called ureide pathway, nitrogen is released as ammonia from allantoate through a series of reactions starting with allantoate amidohydrolase (AAH), a manganese-dependent enzyme found in plants and bacteria. We report NMR evidence that the true product of the AAH reaction is S-ureidoglycine, a nonstandard alpha-amino acid that spontaneously releases ammonia in vitro. Using gene proximity and logical genome analysis, we identified a candidate gene (ylbA) for S-ureidoglycine metabolism. The proteins encoded by Escherichia coli and Arabidopsis thaliana genes catalyze the manganese-dependent release of ammonia through hydrolysis of 5-ureidoglycine. Hydrolysis then inverts the configuration and yields 5-ureidoglycolate. S-Ureldoglycine aminohydrolase (UGHY) is cytosolic in bacteria, whereas in plants it is localized, like allantoate amidohydrolase, in the endoplasmic reticulum. These findings strengthen the basis for the known sensitivity of the ureide pathway to Mn availability and suggest a further rationale for the active transport of Mn in the endoplasmic reticulum of plant cells.
• Reversible activation of allantoate amidohydrolase by acid-pretreatment and other properties of the enzyme
  作者：G.D. Vogels

  DOI：10.1016/s0926-6593(66)80067-x

  日期：1966.1