pyroglutamate

• 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: pyroglutamate
• 英文别名: (2S)-2-carboxy-3,4-dihydro-2H-pyrrol-5-olate
• 化学式: C₅H₆NO₃
• 分子量: 128.108
• InChiKey: ODHCTXKNWHHXJC-VKHMYHEASA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  69.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  pyroglutamate 在 水 作用下， 生成 2-氨基戊二酸酯
  参考文献：
  名称：

  水质子NMR检测酰胺水解和二甘氨酸二聚化†

  摘要：

  发现水质子R 2（1 H 2 O）的横向弛豫速率对酰胺水解和二甘氨酸二聚化敏感。结果证明了使用R 2（1 H 2 O）作为诊断工具检测水溶液中化学变化的可行性。潜在的应用包括药品配方和检查。

  DOI：

  10.1039/c8cc03935f
• 作为产物：
  描述：

  an α-(γ-L-glutamyl)-L-amino acid 生成 pyroglutamate 、 an L-α-amino acid
  参考文献：
  名称：

  The Identification and Structural Characterization of C7orf24 as γ-Glutamyl Cyclotransferase

  摘要：

  The hypothetical protein C7orf24 has been implicated as a cancer marker with a potential role in cell proliferation. We have identified C7orf24 as gamma-glutamyl cyclotransferase (GGCT) that catalyzes the formation of 5-oxoproline (pyroglutamic acid) from gamma-glutamyl dipeptides and potentially plays a significant role in glutathione homeostasis. In the present study we have identified the first cDNA clones encoding a gamma-glutamyl cyclotransferase. The GGCT gene is located on chromosome 7p14-15 and consists of four exons that span 8 kb. The primary sequence is 188 amino acids in length and is unlike any protein of known function. We crystallized functional recombinant gamma-glutamyl cyclotransferase and determined its structure at 1.7 angstrom resolution. The enzyme is a dimer of 20,994-Da subunits. The topology of GGCT is unrelated to other enzymes associated with cyclotransferase-like activity. The fold was originally classified as "BtrG-like," a small family that only includes structures of hypothetical proteins from Mus musculus, Escherichia coli, Pyrococcus horikoshii, and Arabidopsis thaliana. Since this is the first member of this family with a defined function, we propose to refer to this structure as the gamma-glutamyl cyclotransferase fold. We have identified a potential active site pocket that contains a highly conserved glutamic acid (Glu(98)) and propose that it acts as a general acid/base in the reaction mechanism. Mutation of Glu(98) to Ala or Gln completely inactivates the enzyme without altering the overall fold.

  DOI：

  10.1074/jbc.m803623200

文献信息

• SALTS OF LORCASERIN WITH OPTICALLY ACTIVE ACIDS
  申请人：Blackburn Anthony C.

  公开号：US20130310369A1

  公开（公告）日：2013-11-21

  Salts of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine with optically active acids, and pharmaceutical compositions comprising them that are useful for, inter alia, weight management.

  8-氯-1-甲基-2,3,4,5-四氢-1H-3-苯并嗪的盐，与手性酸混合制成的药物组合物，可用于体重管理等用途。
• Salts of lorcaserin with optically active acids
  申请人：Blackburn Anthony C.

  公开号：US09248133B2

  公开（公告）日：2016-02-02

  Salts of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine with optically active acids, and pharmaceutical compositions comprising them that are useful for, inter alia, weight management.

  含有手性酸的8-氯-1-甲基-2,3,4,5-四氢-1H-3-苯并嗪盐，以及包含它们的药物组合物，可用于体重管理等用途。
• OXP1/YKL215c encodes an ATP-dependent 5-oxoprolinase in Saccharomyces cerevisiae: functional characterization, domain structure and identification of actin-like ATP-binding motifs in eukaryotic 5-oxoprolinases
  作者：Akhilesh Kumar、Anand Kumar Bachhawat

  DOI：10.1111/j.1567-1364.2010.00619.x

  日期：——

  OXP1/YKL215c, an uncharacterized ORF of Saccharomyces cerevisiae, encodes a functional ATP-dependent 5-oxoprolinase of 1286 amino acids. The yeast 5-oxoprolinase activity was demonstrated in vivo by utilization of 5-oxoproline as a source of glutamate and OTC, a 5-oxoproline sulfur analogue, as a source of sulfur in cells overexpressing OXP1. In vitro characterization by expression and purification of the recombinant protein in S. cerevisiae revealed that the enzyme exists and functions as a dimer, and has a Km of 159 μM and a Vmax of 3.5 nmol h−1 μg−1 protein. The enzyme was found to be functionally separable in two distinct domains. An ‘actin-like ATPase motif’ could be identified in 5-oxprolinases, and mutation of key residues within this motif led to complete loss in ATPase and 5-oxoprolinase activity of the enzyme. The results are discussed in the light of the previously postulated truncated γ-glutamyl cycle of yeasts.

  OXP1/YKL215c 是酵母菌（Saccharomyces cerevisiae）中一个未表征的 ORF，它编码一个由 1286 个氨基酸组成的功能性 ATP 依赖性 5-氧代脯氨酸酶。通过在过表达 OXP1 的细胞中利用 5-氧代脯氨酸作为谷氨酸的来源和利用 5-氧代脯氨酸硫类似物 OTC 作为硫的来源，证明了酵母 5-氧代脯氨酸酶的体内活性。通过在 S. cerevisiae 中表达和纯化重组蛋白进行体外表征发现，该酶以二聚体形式存在并发挥功能，其 Km 为 159 μM，Vmax 为 3.5 nmol h-1 μg-1 蛋白。研究发现，该酶在功能上可分为两个不同的域。在 5-oxprolinases 中可以发现一个 "类肌动蛋白 ATPase 基团"，该基团中关键残基的突变导致该酶完全丧失 ATPase 和 5-oxoprolinase 活性。本文根据先前推测的酵母菌截短的γ-谷氨酰循环对这一结果进行了讨论。
• Enzymatic Conversion of 5-Oxo-L-Proline (L-Pyrrolidone Carboxylate) to L-Glutamate Coupled with Cleavage of Adenosine Triphosphate to Adenosine Diphosphate, a Reaction in the γ-Glutamyl Cycle
  作者：Paul Van Der Werf、Marian Orlowski、Alton Meister

  DOI：10.1073/pnas.68.12.2982

  日期：1971.12

  5-oxo-L-proline (L-5-oxo-pyrrolidine-2-carboxylic acid, L-2-pyrrolidone-5-carboxylic acid, L-pyroglutamic acid) to L-glutamic acid, with concomitant stoichiometric cleavage of ATP to ADP and orthophosphate. The reaction catalyzed by 5-oxoprolinase, in which 5-oxoproline formed from gamma-glutamyl amino acids by the action of gamma-glutamylcyclotransferase is converted to glutamate, appears to function in the gamma-glutamyl

  在大鼠肾脏和其他一些组织中发现了一种新的酶5-氧脯氨酸酶。它催化5-氧代-L-脯氨酸（L-5-氧代-吡咯烷-2-羧酸，L-2-吡咯烷酮-5-羧酸，L-焦谷氨酸）向L-谷氨酸的转化ATP对ADP和正磷酸盐的化学计量切割。由5-氧脯氨酸酶催化的反应似乎在γ-谷氨酰基循环中起作用，其中由γ-谷氨酰基环转移酶的作用由γ-谷氨酰基氨基酸形成的5-氧代脯氨酸转化为谷氨酸。5-羟脯氨酸酶需要Mg（++）（或Mn（++））和K（+）（或NH（4）（+））才能起作用。该平衡明显有利于在pH 7.8下形成谷氨酸。
• gamma-Glutamylamine cyclotransferase: specificity toward epsilon-(L-gamma-glutamyl)-L-lysine and related compounds.
  作者：M L Fink、S I Chung、J E Folk

  DOI：10.1073/pnas.77.8.4564

  日期：1980.8

  gamma-Glutamylamine cyclotransferase, an enzyme that catalyzes the conversion of L-gamma-glutamylamines to free amines and 5-oxo-L-proline, was found in rabbit kidney and in various other tissues. The specificity of this enzyme indicates that it functions in the metabolism of products of transglutaminase action; among its substrates are epsilon-(L-gamma-glutamyl)-L-lysine, a derivative of this peptide in which the alpha-amino and carboxyl groups of the lysine moiety are blocked, and L-gamma-glutamyl-polyamine derivatives.

  γ-谷氨酰胺环转移酶是一种酶，它催化L-γ-谷氨酰胺转化为自由胺和5-氧代-L-脯氨酸，在兔肾和其他各种组织中发现。该酶的特异性表明它在转谷氨酰酶作用产物的代谢中起作用；它的底物包括ε-(L-γ-谷氨酰)-L-赖氨酸，这是该肽的一个衍生物，其中赖氨酸部分的α-氨基和羧基被阻断，以及L-γ-谷氨酰多胺衍生物。