Allantoate

• 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: Allantoate
• 英文别名: 2,2-bis(carbamoylamino)acetate
• 化学式: C4H7N4O4-
• 分子量: 175.12
• InChiKey: NUCLJNSWZCHRKL-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  150
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Allantoate 、 水 生成 (-)-Ureidoglycolate 、 尿素
  参考文献：
  名称：

  Crystal Structure of Yeast Allantoicase Reveals a Repeated Jelly Roll Motif

  摘要：

  Allantoicase (EC 3.5.3.4) catalyzes the conversion of allantoate into ureidoglycolate and urea, one of the final steps in the degradation of purines to urea. The mechanism of most enzymes involved in this pathway, which has been known for a long time, is unknown. In this paper we describe the three-dimensional crystal structure of the yeast allantoicase determined at a resolution of 2.6 A by single anomalous diffraction. This constitutes the first structure for an enzyme of this pathway. The structure reveals a repeated jelly roll beta-sheet motif, also present in proteins of unrelated biochemical function. Allantoicase has a hexameric arrangement in the crystal (dimer of trimers). Analysis of the protein sequence against the structural data reveals the presence of two totally conserved surface patches, one on each jelly roll motif. The hexameric packing concentrates these patches into conserved pockets that probably constitute the active site.

  DOI：

  10.1074/jbc.m401336200
• 作为产物：
  描述：

  (S)-(+)-allantoin 、 水 生成 Allantoate 、 氢(+1)阳离子
  参考文献：
  名称：

  Functional Expression and Characterization of the Two Cyclic Amidohydrolase Enzymes, Allantoinase and a Novel Phenylhydantoinase, from Escherichia coli

  摘要：

  摘要 根据相关酶相同位置上的刚性保守结构域，最近提出了一个环酰胺水解酶超家族，包括二氢嘧啶酶、尿囊素酶、海因酶和二氢烟酸酶，它们都参与嘌呤和嘧啶环的代谢。有了这些保守结构域，两个来自 大肠杆菌 从大肠杆菌的基因组序列中发现了两个推定的环酰胺水解酶基因，其两侧有相关的基因。从大肠杆菌的基因组序列中 大肠杆菌 的 allB 基因和一个推测的开放阅读框（暂定为 hyuA (代表海因利用酶）基因被预测为表达水解酶。与 allB 相比，高水平表达 hyuA 在 大肠杆菌中 即使在不同的诱导条件下，也无法成功表达单一蛋白。我们将 HyuA 表达为麦芽糖结合蛋白融合蛋白，将 AllB 表达为其原生形式，然后通过常规程序纯化了它们。 AllB 编码一个四聚体尿囊素酶（453 个氨基酸），它能将嘌呤代谢物尿囊素水解为尿囊酸。另一个开放阅读框 hyuA 在物理图谱上位于 64.4 分钟附近，被称为 UUG 起点，其编码为 d -甾体特异性苯海因酶（465 个氨基酸）的编码，该酶是一个同源四聚体。这是一种属于环酰胺水解酶超家族的新型酶、 大肠杆菌 苯海因酶对 5′位芳香侧链的海因衍生物具有独特的活性，但不容易水解简单的环状脲苷。推导出的新型苯基海因酶的氨基酸序列与尿囊素酶和二氢嘧啶酶的氨基酸序列具有显著的同源性（45%），但其功能作用仍有待阐明。尽管 HyuA 的生理功能尚不明确，但它与利用尿囊素的 AllB 的存在强烈表明，环状脲苷可能被大肠杆菌利用为营养源。 大肠杆菌 .

  DOI：

  10.1128/jb.182.24.7021-7028.2000

文献信息

• 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.
• Crystal structure of an allantoicase (YIR029W) from Saccharomyces cerevisiae at 2.4 Å resolution
  作者：Qingping Xu、Robert Schwarzenbacher、Rebecca Page、Eric Sims、Polat Abdubek、Eileen Ambing、Tanya Biorac、Linda S. Brinen、Jamison Cambell、Jaume M. Canaves、Hsiu-Ju Chiu、Xiaoping Dai、Ashley M. Deacon、Mike DiDonato、Marc-André Elsliger、Ross Floyd、Adam Godzik、Carina Grittini、Slawomir K. Grzechnik、Eric Hampton、Lukasz Jaroszewski、Cathy Karlak、Heath E. Klock、Eric Koesema、John S. Kovarik、Andreas Kreusch、Peter Kuhn、Scott A. Lesley、Inna Levin、Daniel McMullan、Timothy M. McPhillips、Mitchell D. Miller、Andrew Morse、Kin Moy、Jie Ouyang、Kevin Quijano、Ron Reyes、Fred Rezezadeh、Alyssa Robb、Glen Spraggon、Raymond C. Stevens、Henry van den Bedem、Jeff Velasquez、Juli Vincent、Frank von Delft、Xianhong Wang、Bill West、Guenter Wolf、Keith O. Hodgson、John Wooley、Ian A. Wilson

  DOI：10.1002/prot.20164

  日期：——
• Hydrolysis, racemization and absolute configuration of ureidoglycolate, a substrate of allantoicase
  作者：E.J. 's-Gravenmade、G.D. Vogels、C. Van der Drift

  DOI：10.1016/0005-2744(70)90134-8

  日期：1970.3
• Crystal Structure of Metal-Dependent Allantoinase from Escherichia coli
  作者：Kwangsoo Kim、Myung-Il Kim、Jiwoung Chung、Joong-Hoon Ahn、Sangkee Rhee

  DOI：10.1016/j.jmb.2009.02.041

  日期：2009.4

  Allantoinase acts as a key enzyme for the biogenesis and degradation of ureides by catalyzing the conversion of (S)-allantoin into allantoate, the final step in the ureide pathway. Despite limited sequence similarity, biochemical studies of the enzyme suggested that allantoinase belongs to the amidohydrolase family. In this study, the crystal structure of allantoinase from Escherichia coli was determined at 2.1 A resolution. The enzyme consists of a homotetramer in which each monomer contains two domains: a pseudo-triosephosphate-isomerase barrel and a beta-sheet. Analogous to other enzymes in the amidohydrolase family, allantoinase retains a binuclear metal center in the active site, embedded within the barrel fold. Structural analyses demonstrated that the metal ions in the active site ligate one hydroxide and six residues that are conserved among allantoinases from other organisms. Functional analyses showed that the presence of zinc in the metal center is essential for catalysis and enantioselectivity of substrate. Both the metal center and active site residues Asn94 and Ser317 play crucial roles in dictating enzyme activity. These structural and functional features are distinctively different from those of the metal-independent allantoinase, which was very recently identified.