L-Fuconate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 英文名称: L-Fuconate
• 英文别名: (2S,3R,4R,5S)-2,3,4,5-tetrahydroxyhexanoate
• 化学式: C6H11O6-
• 分子量: 179.15
• InChiKey: NBFWIISVIFCMDK-RSJOWCBRSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  121
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  L-Fuconate 生成 2-Dehydro-3-deoxy-L-fuconate 、 水
  参考文献：
  名称：

  L-Fucose Metabolism in Mammals. I. Pork Liver L-Fuconate Hydro-lyase

  摘要：

  猪肝已被证明含有可溶性酶L-岩藻糖醇脱水酶（L-岩藻糖醇脱水酶），能够将L-岩藻糖醇脱水为2-酮-3-脱氧-L-岩藻糖醇。该酶已部分纯化。L-岩藻糖醇的K_m为1.0毫摩尔；D-阿拉伯糖也是一个优秀的底物（K_m为1.3毫摩尔），但该酶对D-岩藻糖醇、L-阿拉伯糖、D-葡萄糖酸、D-古龙酸、D-半乳糖酸、L-曼果酸和D-葡萄糖醛酸无活性。该酶在pH 7.0处具有明显的pH最适值，需要Mg²⁺才能发挥活性，并受对羟基汞苯甲酸的抑制。L-岩藻糖醇脱水酶的底物特异性类似于猪肝L-岩藻糖：NAD氧化还原酶，建议这些酶通过以下途径参与L-岩藻糖的代谢：L-岩藻糖→L-岩藻糖内酯→L-岩藻糖醇→2-酮-3-脱氧-L-岩藻糖醇。后者的代谢命运尚不清楚。D-阿拉伯糖可以通过类似的途径被猪肝代谢。

  DOI：

  10.1139/o72-111

文献信息

• <scp>L</scp>-Fucose Metabolism in Mammals. I. Pork Liver <scp>L</scp>-Fuconate Hydro-lyase
  作者：Raymond Yuen、Harry Schachter

  DOI：10.1139/o72-111

  日期：1972.7.1

  Pork liver has been shown to contain a soluble enzyme, L-fuconate hydro-lyase (L-fuconate dehydratase), capable of dehydrating L-fuconate to 2-keto-3-deoxy-L-fuconate. The enzyme has been partially purified. The K_m for L-fuconate is 1.0 mM; D-arabonate is also an excellent substrate (K_m 1.3 mM) but the enzyme is inactive with D-fuconate, L-arabonate, D-gluconate, D-gulonate, D-galactonate, L-mannonate, and D-glucuronate. The enzyme has a sharp pH optimum at pH 7.0, requires Mg²⁺ for activity, and is inhibited by p-hydroxymercuribenzoate. The substrate specificity of L-fuconate hydro-lyase resembles that of pork liver L-fucose: NAD oxidoreductase and it is suggested that these enzymes serve in the metabolism of L-fucose by the following pathway: L-fucose → L-fucono-1,5-lactone → L-fuconate → 2-keto-3-deoxy-L-fuconate. The metabolic fate of the latter compound is not known. D-Arabinose can be metabolized by pork liver by an analogous pathway.

  猪肝已被证明含有可溶性酶L-岩藻糖醇脱水酶（L-岩藻糖醇脱水酶），能够将L-岩藻糖醇脱水为2-酮-3-脱氧-L-岩藻糖醇。该酶已部分纯化。L-岩藻糖醇的K_m为1.0毫摩尔；D-阿拉伯糖也是一个优秀的底物（K_m为1.3毫摩尔），但该酶对D-岩藻糖醇、L-阿拉伯糖、D-葡萄糖酸、D-古龙酸、D-半乳糖酸、L-曼果酸和D-葡萄糖醛酸无活性。该酶在pH 7.0处具有明显的pH最适值，需要Mg²⁺才能发挥活性，并受对羟基汞苯甲酸的抑制。L-岩藻糖醇脱水酶的底物特异性类似于猪肝L-岩藻糖：NAD氧化还原酶，建议这些酶通过以下途径参与L-岩藻糖的代谢：L-岩藻糖→L-岩藻糖内酯→L-岩藻糖醇→2-酮-3-脱氧-L-岩藻糖醇。后者的代谢命运尚不清楚。D-阿拉伯糖可以通过类似的途径被猪肝代谢。
• Evolution of Enzymatic Activities in the Enolase Superfamily:  <scp>l</scp>-Fuconate Dehydratase from <i>Xanthomonas campestris</i>^,
  作者：Wen Shan Yew、Alexander A. Fedorov、Elena V. Fedorov、John F. Rakus、Richard W. Pierce、Steven C. Almo、John A. Gerlt

  DOI：10.1021/bi061687o

  日期：2006.12.1

  Many members of the mechanistically diverse enolase superfamily have unknown functions. In this report we use both genome (operon) context and screening of a library of acid sugars to assign the L-fuconate dehydratase (FucD) function to a member of the mandelate racemase (MR) subgroup of the superfamily encoded by the Xanthomonas campestris pv. campestris str. ATCC 33913 genome (GI:21233491). Orthologues of FucD are found in both bacteria and eukaryotes, the latter including the rTS beta protein in Homo sapiens that has been implicated in regulating thymidylate synthase activity. As suggested by sequence alignments and confirmed by high-resolution structures in the presence of active site ligands, FucD and MR share the same active site motif of functional groups: three carboxylate ligands for the essential Mg2+ located at the ends of the third, fourth, and fifth beta-strands in the (beta/alpha)7beta-barrel domain (Asp 248, Glu 274, and Glu 301, respectively), a Lys-x-Lys motif at the end of the second beta-strand (Lys 218 and Lys 220), a His-Asp dyad at the end of the seventh and beta-strands (His 351 and Asp 324, respectively), and a Glu at the end of the eighth beta-strand (Glu 382). The mechanism of the FucD reaction involves initial abstraction of the 2-proton by Lys 220, acid catalysis of the vinylogous beta-elimination of the 3-OH group by His 351, and stereospecific ketonization of the resulting enol, likely by the conjugate acid of Lys 220, to yield the 2-keto-3-deoxy-L-fuconate product. Screening of the library of acid sugars revealed substrate and functional promiscuity: In addition to L-fuconate, FucD also catalyzes the dehydration of L-galactonate, D-arabinonate, D-altronate, L-talonate, and D-ribonate. The dehydrations of L-fuconate, L-galactonate, and D-arabinonate are initiated by abstraction of the 2-protons by Lys 220. The dehydrations of L-talonate and D-ribonate are initiated by abstraction of the 2-protons by His 351; however, protonation of the enediolate intermediates by the conjugate acid of Lys 220 yields L-galactonate and D-arabinonate in competition with dehydration. The functional promiscuity discovered for FucD highlights possible structural mechanisms for evolution of function in the enolase superfamily.
• Enzymatic and Structural Characterization of rTSγ Provides Insights into the Function of rTSβ
  作者：Daniel J. Wichelecki、D. Sean Froese、Jolanta Kopec、Joao R.C. Muniz、Wyatt W. Yue、John A. Gerlt

  DOI：10.1021/bi500349e

  日期：2014.4.29

  In humans, the gene encoding a reverse thymidylate synthase (rTS) is transcribed in the reverse direction of the gene encoding thymidylate synthase (TS) that is involved in DNA biosynthesis. Three isoforms are found: alpha, beta, and gamma, with the transcript of the alpha-isoform overlapping with that of TS. rTS beta has been of interest since the discovery of its overexpression in methotrexate and 5-fluorouracil resistant cell lines. Despite more than 20 years of study, none of the rTS isoforms have been biochemically or structurally characterized. In this study, we identified rTS gamma as an L-fuconate dehydratase and determined its high-resolution crystal structure. Our data provide an explanation for the observed difference in enzymatic activities between rTS beta and rTS gamma, enabling more informed proposals for the possible function of rTS beta in chemotherapeutic resistance.