L-Leu-D-Glu | 38062-67-8

• 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: L-Leu-D-Glu
• 英文别名: L-Leu-D-Glu-OH；(2R)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]pentanedioic acid
• CAS: 38062-67-8
• 化学式: C₁₁H₂₀N₂O₅
• 分子量: 260.29
• InChiKey: NFNVDJGXRFEYTK-JGVFFNPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.3
• 重原子数：
  18
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.73
• 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：

  L-Leu-D-Glu 在 recombinant Streptomyces coelicolor Sco₃₀₅₈ dipeptidase 、 水 作用下， 生成 L-亮氨酸 、 D-谷氨酸
  参考文献：
  名称：

  Structure, Mechanism, and Substrate Profile for Sco3058: The Closest Bacterial Homologue to Human Renal Dipeptidase,

  摘要：

  Human renal dipeptidase, an enzyme associated With glutathione metabolism and the hydrolysis of beta-lactams, is similar in sequence to a cluster of similar to 400 microbial proteins currently annotated as nonspecific dipeptidases within the amidohydrolase superfamily. The closest homologue to the human renal dipeptidase from a Fully sequenced microbe is Sco3058 from Streptomyces coelicolor. Dipeptide Substrates of Sco3058 were identified by screening a comprehensive series Of L-Xaa-L-Xaa, L-Xaa-D-Xaa, and D-Xaa-L-Xaa dipeptide libraries. The substrate specificity profile shows that Sco3058 hydrolyzes a broad range of dipeptides with a marked preference for all L-amino acid at the N-terminus and a D-amino acid at the C-terminus. The best Substrate identified was L-Arg-D-Asp (k(eat)/K-m = 7.6 x 10(5) M-1 s(-1)). The three-dimensional structure of Sco3058 was determined in the absence and presence of the inhibitors citrate and a phosphinate mimic Of L-Ala-D-Asp. The enzyme folds as (beta/alpha)(8) barrel, and two zinc Ions are bound in the active site. Site-directed mutagenesis was used to probe the importance of specific residues that have direct interactions with the substrate analogues in the active site (Asp-22, His-150, Arg-223, and Asp-320). The solvent viscosity and kinetic effects of D2O indicate that Substrate binding is relatively sticky and that proton transfers do not occur during the rate-limiting step. A bell-shaped pH-rate profile for k(cat) and k(cat)/k(m) indicated that one group needs to he deprotonated and a second group Must be protonated for optimal turnover. Computational docking of high-energy intermediate forms Of L/D-Ala-L/D-Ala to the three-dimensional Structure of Sco3058 identified the Structural determinants for the stereochemical preferences for Substrate binding and turnover.

  DOI：

  10.1021/bi901935y

文献信息

• Structure, Mechanism, and Substrate Profile for Sco3058: The Closest Bacterial Homologue to Human Renal Dipeptidase,
  作者：Jennifer A. Cummings、Tinh T. Nguyen、Alexander A. Fedorov、Peter Kolb、Chengfu Xu、Elena V. Fedorov、Brian K. Shoichet、David P. Barondeau、Steven C. Almo、Frank M. Raushel

  DOI：10.1021/bi901935y

  日期：2010.1.26

  Human renal dipeptidase, an enzyme associated With glutathione metabolism and the hydrolysis of beta-lactams, is similar in sequence to a cluster of similar to 400 microbial proteins currently annotated as nonspecific dipeptidases within the amidohydrolase superfamily. The closest homologue to the human renal dipeptidase from a Fully sequenced microbe is Sco3058 from Streptomyces coelicolor. Dipeptide Substrates of Sco3058 were identified by screening a comprehensive series Of L-Xaa-L-Xaa, L-Xaa-D-Xaa, and D-Xaa-L-Xaa dipeptide libraries. The substrate specificity profile shows that Sco3058 hydrolyzes a broad range of dipeptides with a marked preference for all L-amino acid at the N-terminus and a D-amino acid at the C-terminus. The best Substrate identified was L-Arg-D-Asp (k(eat)/K-m = 7.6 x 10(5) M-1 s(-1)). The three-dimensional structure of Sco3058 was determined in the absence and presence of the inhibitors citrate and a phosphinate mimic Of L-Ala-D-Asp. The enzyme folds as (beta/alpha)(8) barrel, and two zinc Ions are bound in the active site. Site-directed mutagenesis was used to probe the importance of specific residues that have direct interactions with the substrate analogues in the active site (Asp-22, His-150, Arg-223, and Asp-320). The solvent viscosity and kinetic effects of D2O indicate that Substrate binding is relatively sticky and that proton transfers do not occur during the rate-limiting step. A bell-shaped pH-rate profile for k(cat) and k(cat)/k(m) indicated that one group needs to he deprotonated and a second group Must be protonated for optimal turnover. Computational docking of high-energy intermediate forms Of L/D-Ala-L/D-Ala to the three-dimensional Structure of Sco3058 identified the Structural determinants for the stereochemical preferences for Substrate binding and turnover.