N-acetyl-D-mannosamino-lactone

• 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: N-acetyl-D-mannosamino-lactone
• 英文别名: N-acetylmannosaminolactone；N-Acetyl-D-mannosaminolactone；N-[(3S,4R,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-2-oxooxan-3-yl]acetamide
• 化学式: C₈H₁₃NO₆
• 分子量: 219.194
• InChiKey: NELQYZRSPDCGRQ-XZBKPIIZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  116
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-acetyl-D-mannosamino-lactone 在 水 作用下， 生成 N-acetylmannosaminic acid
  参考文献：
  名称：

  Crystal structures and functional studies clarify substrate selectivity and catalytic residues for the unique orphan enzyme N-acetyl-D-mannosamine dehydrogenase

  摘要：

  NAMDH（N-乙酰-D-甘露糖胺脱氢酶）来自土壤细菌黄杆菌（Flavobacterium sp. 141-8），它催化一种罕见的依赖 NAD+ 的 ManNAc（N-乙酰-D-甘露糖胺）氧化为 N-乙酰甘露糖胺内酯，后者自发水解为 N-乙酰甘露糖胺酸。NAMDH 属于 SDR（短链脱氢酶/还原酶）超家族，是迄今为止唯一具有特征的 NAMDH。为了更好地了解这种独特酶的结构和生化特性，我们进行了全面的功能、稳定性、定点诱变和晶体学研究。NAMDH 具有显著的碱性 pH 最适值（pH 9.4），在甘氨酸缓冲液中具有较高的热稳定性（Tm=64°C），对 ManNAc 和 NAD+ 具有严格的选择性。无配体以及与 ManNAc 和 NAD+ 结合的酶的晶体结构显示，该酶是一个具有 222 点对称性的紧凑同源四聚体，由呈现特征性 SDR α3β7α3 "三明治 "折叠的亚基组成。高度发达的 C 端尾部用作连接附近亚基的闩锁，从而稳定了四聚体。与底物的极性相互作用形成了一个密集的网络，包括将其乙酰氨基包裹在一个特定的结合袋中，以及糖 4OH 原子的氢结合，确保了对 ManNAc 的特异性。NAMDH 底物复合物和定点突变研究确定了催化四聚体，并为确定新的 NAMDH 序列提供了有用的特征。

  DOI：

  10.1042/bj20140266
• 作为产物：
  描述：

  D-GlcNAc 在 bacterial β-N-acetyl-hexosaminidase from Zobellia galactanivorans 、 bacterial N-acetylglucosamine 2-epimerase 、 N-acetyl-D-mannosamine dehydrogenase 、 β-烟酰胺腺嘌呤二核苷酸 作用下， 以 乙腈 、 aq. phosphate buffer 为溶剂， 反应 1.25h， 生成 N-acetyl-D-mannosamino-lactone
  参考文献：
  名称：

  Chemo-enzymatic approach to access diastereopure α-substituted GlcNAc derivatives

  摘要：

  The formation of diastereopure -substituted GlcNAc derivatives in a simple and straightforward way is a challenging task. Herein, we report the chemical synthesis of diastereomeric /-substituted GlcNAc derivatives under non-anhydrous atmosphere using unprotected GlcNAc, followed by a selective enzymatic hydrolysis step using a bacterial N-acetyl-hexosaminidase to provide only -substituted GlcNAc. This enzyme proved to selectively hydrolyze the -anomeric GlcNAc derivatives, while the -anomeric GlcNAc derivatives remained unreacted. The released GlcNAc (and therefore the / ratios) could be quantified using a coupled enzymatic assay consisting of GlcNAc 2-epimerase and N-acetyl- mannosamine dehydrogenase in a simple and accurate way.

  DOI：

  10.1080/07328303.2017.1321116

文献信息

• Chemo-enzymatic approach to access diastereopure α-substituted GlcNAc derivatives
  作者：Su-Yan Wang、Pedro Laborda、Ai-Min Lu、Meng Wang、Xu-Chu Duan、Li Liu、Josef Voglmeir

  DOI：10.1080/07328303.2017.1321116

  日期：2016.11.21

  The formation of diastereopure -substituted GlcNAc derivatives in a simple and straightforward way is a challenging task. Herein, we report the chemical synthesis of diastereomeric /-substituted GlcNAc derivatives under non-anhydrous atmosphere using unprotected GlcNAc, followed by a selective enzymatic hydrolysis step using a bacterial N-acetyl-hexosaminidase to provide only -substituted GlcNAc. This enzyme proved to selectively hydrolyze the -anomeric GlcNAc derivatives, while the -anomeric GlcNAc derivatives remained unreacted. The released GlcNAc (and therefore the / ratios) could be quantified using a coupled enzymatic assay consisting of GlcNAc 2-epimerase and N-acetyl- mannosamine dehydrogenase in a simple and accurate way.
• Crystal structures and functional studies clarify substrate selectivity and catalytic residues for the unique orphan enzyme <i>N</i>-acetyl-<scp>D</scp>-mannosamine dehydrogenase
  作者：Agustín Sola-Carvajal、Fernando Gil-Ortiz、Francisco García-Carmona、Vicente Rubio、Álvaro Sánchez-Ferrer

  DOI：10.1042/bj20140266

  日期：2014.9.15

  NAMDH (N-acetyl-D-mannosamine dehydrogenase), from the soil bacteroidete Flavobacterium sp. 141-8, catalyses a rare NAD+-dependent oxidation of ManNAc (N-acetyl-D-mannosamine) into N-acetylmannosamino-lactone, which spontaneously hydrolyses into N-acetylmannosaminic acid. NAMDH belongs to the SDR (short-chain dehydrogenase/reductase) superfamily and is the only NAMDH characterized to date. Thorough functional, stability, site-directed mutagenesis and crystallographic studies have been carried out to understand better the structural and biochemical aspects of this unique enzyme. NAMDH exhibited a remarkable alkaline pH optimum (pH 9.4) with a high thermal stability in glycine buffer (Tm=64°C) and a strict selectivity towards ManNAc and NAD+. Crystal structures of ligand-free and ManNAc- and NAD+-bound enzyme forms revealed a compact homotetramer having point 222 symmetry, formed by subunits presenting the characteristic SDR α3β7α3 sandwich fold. A highly developed C-terminal tail used as a latch connecting nearby subunits stabilizes the tetramer. A dense network of polar interactions with the substrate including the encasement of its acetamido group in a specific binding pocket and the hydrogen binding of the sugar 4OH atom ensure specificity for ManNAc. The NAMDH–substrate complexes and site-directed mutagenesis studies identify the catalytic tetrad and provide useful traits for identifying new NAMDH sequences.

  NAMDH（N-乙酰-D-甘露糖胺脱氢酶）来自土壤细菌黄杆菌（Flavobacterium sp. 141-8），它催化一种罕见的依赖 NAD+ 的 ManNAc（N-乙酰-D-甘露糖胺）氧化为 N-乙酰甘露糖胺内酯，后者自发水解为 N-乙酰甘露糖胺酸。NAMDH 属于 SDR（短链脱氢酶/还原酶）超家族，是迄今为止唯一具有特征的 NAMDH。为了更好地了解这种独特酶的结构和生化特性，我们进行了全面的功能、稳定性、定点诱变和晶体学研究。NAMDH 具有显著的碱性 pH 最适值（pH 9.4），在甘氨酸缓冲液中具有较高的热稳定性（Tm=64°C），对 ManNAc 和 NAD+ 具有严格的选择性。无配体以及与 ManNAc 和 NAD+ 结合的酶的晶体结构显示，该酶是一个具有 222 点对称性的紧凑同源四聚体，由呈现特征性 SDR α3β7α3 "三明治 "折叠的亚基组成。高度发达的 C 端尾部用作连接附近亚基的闩锁，从而稳定了四聚体。与底物的极性相互作用形成了一个密集的网络，包括将其乙酰氨基包裹在一个特定的结合袋中，以及糖 4OH 原子的氢结合，确保了对 ManNAc 的特异性。NAMDH 底物复合物和定点突变研究确定了催化四聚体，并为确定新的 NAMDH 序列提供了有用的特征。