β-aspartyl-leucine

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: β-aspartyl-leucine
• 英文别名: L-beta-aspartyl-L-leucine；β-Asp-Leu；H-Asp(Leu-OH)-OH；(2S)-2-[[(3S)-3-amino-3-carboxypropanoyl]amino]-4-methylpentanoic acid
• 化学式: C₁₀H₁₈N₂O₅
• mdl: MFCD00057845
• 分子量: 246.263
• InChiKey: IYJILWQAFPUBHP-BQBZGAKWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.8
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  130
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  β-aspartyl-leucine 在 HEPES buffer 、 potassium chloride 作用下， 以 水 为溶剂， 生成 L-亮氨酸 、 L-天门冬氨酸
  参考文献：
  名称：

  Functional significance of Glu-77 and Tyr-137 within the active site of isoaspartyl dipeptidase

  摘要：

  Isoaspartyl dipeptidase (IAD) is a binuclear metalloenzyme and a member of the amidohydrolase superfamily. This enzyme catalyzes the hydrolytic cleavage of beta-aspartyl dipeptides. The pH-rate profiles for the hydrolysis of beta-Asp-Leu indicates that catalysis is dependent on the ionization of two groups; one that ionizes at a pH approximately 6 and the other approximately 9. The group that must be ionized for catalysis is directly dependent on the identity of the metal ion bound to the active site. This result is consistent with the ionization of the hydroxide that bridges the two divalent cations. In addition to the residues that interact directly with the divalent cations there are two other residues that are highly conserved and found within the active site: Glu-77 and Tyr-137. Mutation of Tyr-137 to phenylalanine reduced the rate of catalysis by three orders of magnitude. The three dimensional X-ray structure of the Y137F mutant did not show any significant conformation changes relative to the three dimensional structure of the wild-type enzyme. The positioning of the side-chain phenolic group of Tyr-137 in the active site of IAD is consistent with the stabilization of the tetrahedral adduct concomitant with nucleophilic attack by the hydroxide that bridges the two divalent cations. Mutation of Glu-77 resulted in the reduction of catalytic activity by five orders of magnitude. The three dimensional structure of the E77Q mutant did not show any significant conformational changes in the mutant relative to the three dimensional structure of the wild-type enzyme. The positioning of the side-chain carboxylate of Glu-77 is consistent with the formation of an ion pair interaction with the free alpha-amino group of the substrate.

  DOI：

  10.1016/j.bioorg.2005.10.002

文献信息

• COMPOUNDS THAT MODULATE CALCIUM-SENSING RECEPTOR ACTIVITY FOR MODULATING KOKUMI TASTE AND PET FOOD PRODUCTS CONTAINING THE SAME
  申请人：MARS, INCORPORATED

  公开号：US20190274334A1

  公开（公告）日：2019-09-12

  A flavor composition comprising at least one compound that modulates, increases and/or enhances the activity of a calcium-sensing receptor that can be used to enhance the kokumi taste and/or palatability of pet food products is described herein. Also disclosed herein are methods for identifying said compounds.
• [EN] COMPOUNDS THAT MODULATE CALCIUM-SENSING RECEPTOR ACTIVITY FOR MODULATING KOKUMI TASTE AND PET FOOD PRODUCTS CONTAINING THE SAME<br/>[FR] COMPOSÉS QUI MODULENT L'ACTIVITÉ DU RÉCEPTEUR SENSIBLE AU CALCIUM POUR MODULER LE GOÛT KOKUMI ET PRODUITS ALIMENTAIRES POUR ANIMAUX DE COMPAGNIE LES CONTENANT
  申请人：MARS INC

  公开号：WO2017181062A1

  公开（公告）日：2017-10-19

  A flavor composition comprising at least one compound that modulates, increases and/or enhances the activity of a calcium-sensing receptor that can be used to enhance the kokumi taste and/or palatability of pet food products is described herein. Also disclosed herein are methods for identifying said compounds.
• Functional significance of Glu-77 and Tyr-137 within the active site of isoaspartyl dipeptidase
  作者：Ricardo Martí-Arbona、James B. Thoden、Hazel M. Holden、Frank M. Raushel

  DOI：10.1016/j.bioorg.2005.10.002

  日期：2005.12

  Isoaspartyl dipeptidase (IAD) is a binuclear metalloenzyme and a member of the amidohydrolase superfamily. This enzyme catalyzes the hydrolytic cleavage of beta-aspartyl dipeptides. The pH-rate profiles for the hydrolysis of beta-Asp-Leu indicates that catalysis is dependent on the ionization of two groups; one that ionizes at a pH approximately 6 and the other approximately 9. The group that must be ionized for catalysis is directly dependent on the identity of the metal ion bound to the active site. This result is consistent with the ionization of the hydroxide that bridges the two divalent cations. In addition to the residues that interact directly with the divalent cations there are two other residues that are highly conserved and found within the active site: Glu-77 and Tyr-137. Mutation of Tyr-137 to phenylalanine reduced the rate of catalysis by three orders of magnitude. The three dimensional X-ray structure of the Y137F mutant did not show any significant conformation changes relative to the three dimensional structure of the wild-type enzyme. The positioning of the side-chain phenolic group of Tyr-137 in the active site of IAD is consistent with the stabilization of the tetrahedral adduct concomitant with nucleophilic attack by the hydroxide that bridges the two divalent cations. Mutation of Glu-77 resulted in the reduction of catalytic activity by five orders of magnitude. The three dimensional structure of the E77Q mutant did not show any significant conformational changes in the mutant relative to the three dimensional structure of the wild-type enzyme. The positioning of the side-chain carboxylate of Glu-77 is consistent with the formation of an ion pair interaction with the free alpha-amino group of the substrate.