4-[(5'-Adenosyl)(methyl)sulfonio]-2-oxobutanoate

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: 4-[(5'-Adenosyl)(methyl)sulfonio]-2-oxobutanoate
• 英文别名: 4-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-methylsulfonio]-2-oxobutanoate
• 化学式: C₁₅H₁₉N₅O₆S
• 分子量: 397.412
• InChiKey: UOKVQQMBGVMXPU-CJPDYEHRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  178
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  4-[(5'-Adenosyl)(methyl)sulfonio]-2-oxobutanoate 在 sodium tetrahydroborate 作用下， 反应 0.08h， 生成 S-adenosyl-(2-hydroxy-4-methylthio)butanoic acid
  参考文献：
  名称：

  The mechanism of 7,8-diaminopelargonate synthase; the role of S-adenosylmethionine as the amino donor

  摘要：

  由二氨基佩拉尔戈酸（DAPA）合酶催化的反应中，第一个转氨基化步骤的产物已被证明是4-(S-腺苷)-2-氧代丁酸，该产物已被捕获为相应的醇。

  DOI：

  10.1039/b310443p
• 作为产物：
  描述：

  S-腺苷-L-蛋氨酸 在 8-amino-7-oxononanoate 、 diaminopelargonate synthase 作用下， 以 phosphate buffer 为溶剂， 生成 4-[(5'-Adenosyl)(methyl)sulfonio]-2-oxobutanoate
  参考文献：
  名称：

  The mechanism of 7,8-diaminopelargonate synthase; the role of S-adenosylmethionine as the amino donor

  摘要：

  由二氨基佩拉尔戈酸（DAPA）合酶催化的反应中，第一个转氨基化步骤的产物已被证明是4-(S-腺苷)-2-氧代丁酸，该产物已被捕获为相应的醇。

  DOI：

  10.1039/b310443p

文献信息

• Crystal structure of diaminopelargonic acid synthase: evolutionary relationships between pyridoxal-5′-phosphate-dependent enzymes
  作者：Helena Käck、Jenny Sandmark、Katharine Gibson、Gunter Schneider、Ylva Lindqvist

  DOI：10.1006/jmbi.1999.2997

  日期：1999.8

  a non-crystallographic dyad in the crystals, form the homodimeric molecule, which contains two equal active sites. Pyridoxal-5'-phosphate is bound in a cleft formed by both domains of one subunit and the large domain of the second subunit. The cofactor is anchored to the enzyme by a covalent linkage to the side-chain of the invariant residue Lys274. The phosphate group interacts with main-chain nitrogen

  通过X射线晶体学测定，二氨基壬酸合酶（生物素生物合成途径中的一种依赖于维生素B6的酶）的三维结构已确定为1.8 A分辨率。通过使用汞离子衍生化的晶体，通过多波长异常衍射技术解决了该结构。蛋白质模型已精炼到17.5％的结晶R值（不含R的22.6％）。每个酶亚基由两个结构域组成，一个大结构域（残基50-329）包含一个7链主要平行的β-折叠（被α-螺旋包围），一个小结构域包含残基1-49和330-429。与晶体中的非晶体二元组相关的两个亚基形成同二聚体分子，该同二聚体分子包含两个相等的活性位点。吡rid醛-5' -磷酸根结合在由一个亚基的两个结构域和第二亚基的大结构域形成的裂缝中。辅因子通过与不变残基Lys274的侧链的共价连接而锚定在酶上。磷酸基团与位于α-螺旋N末端的Ser113的主链氮原子和侧链相互作用。吡啶氮与不变残基Asp245的侧链形成氢键。在酶的表面转弯时发现了对应于金属离子的电
• The Dual-Specific Active Site of 7,8-Diaminopelargonic Acid Synthase and the Effect of the R391A Mutation
  作者：Andrew C. Eliot、Jenny Sandmark、Gunter Schneider、Jack F. Kirsch

  DOI：10.1021/bi026339a

  日期：2002.10.1

  7,8-Diaminopelargonic acid (DAPA) synthase (EC 2.6.1.62) is a pyridoxal phosphate (PLP)-dependent transaminase that catalyzes the transfer of the (alpha-amino group from S-adenosyl-L-methionine (SAM) to 7-keto-8-aminopelargonic acid (KAPA) to form DAPA in the antepenultimate step in the biosynthesis of biotin. The wild-type enzyme has a steady-state k(cat) value of 0.013 s(-1), and the K-m values for SAM and KAPA are 150 and <2 muM, respectively. The k(max) and apparent K-m values for the half-reaction of the PLP form of the enzyme with SAM are 0.016 s(-1) and 300 muM, respectively, while those for the reaction with DAPA are 0.79 s(-1) and 1 muM. The R391A mutant enzyme exhibits near wild-type kinetic parameters in the reaction with SAM, while the apparent K-m for DAPA is increased 180-fold. The 2.1 Angstrom crystal structure of the R391A mutant enzyme shows that the mutation does not significantly alter the structure. These results indicate that the conserved arginine residue is not required for binding the alpha-amino acid SAM, but it is important for recognition of DAPA.
• Stoner G.L.; Eisenberg M.A., J Biol Chem, 1975, 0021-9258, 4029-36
  作者：Stoner G.L.、Eisenberg M.A.

  DOI：——

  日期：——
• Conserved and Nonconserved Residues in the Substrate Binding Site of 7,8-Diaminopelargonic Acid Synthase from <i>Escherichia coli</i> Are Essential for Catalysis
  作者：Jenny Sandmark、Andrew C. Eliot、Kristoffer Famm、Gunter Schneider、Jack F. Kirsch

  DOI：10.1021/bi0358059

  日期：2004.2.1

  The vitamin B(6)-dependent enzyme 7,8-diaminopelargonic acid (DAPA) synthase catalyzes the antepenultimate step in the synthesis of biotin, the transfer of the alpha-amino group of S-adenosyl-l-methionine (SAM) to 7-keto-8-aminopelargonic acid (KAPA) to form DAPA. The Y17F, Y144F, and D147N mutations in the active site were constructed independently. The k(max)/K(m)(app) values for the half-reaction with DAPA of the Y17F and Y144F mutants are reduced by 1300- and 2900-fold, respectively, compared to the WT enzyme. Crystallographic analyses of these mutants do not show significant changes in the structure of the active site. The kinetic deficiencies, together with a structural model of the enzyme-PLP/DAPA Michaelis complex, point to a role of these two residues in recognition of the DAPA/KAPA substrates and in catalysis. The k(max)/K(m)(app) values for the half-reaction with SAM are similar to that of the WT enzyme, showing that the two tyrosine residues are not involved in this half-reaction. Mutations of the conserved Arg253 uniquely affect the SAM kinetics, thus establishing this position as part of the SAM binding site. The D147N mutant is catalytically inactive in both half-reactions. The structure of this mutant exhibits significant changes in the active site, indicating that this residue plays an important structural role. Of the four residues examined, only Tyr144 and Arg253 are strictly conserved in the available amino acid sequences of DAPA synthases. This enzyme thus provides an illustrative example that active site residues essential for catalysis are not necessarily conserved, i.e., that during evolution alternative solutions for efficient catalysis by the same enzyme arose. Decarboxylated SAM [S-adenosyl-(5')-3-methylthiopropylamine] reacts nearly as well as SAM and cannot be eliminated as a putative in vivo amino donor.
• The mechanism of 7,8-diaminopelargonate synthase; the role of S-adenosylmethionine as the amino donor
  作者：Rachel S. Breen、Dominic J. Campopiano、Scott Webster、Mhairi Brunton、Rory Watt、Robert L. Baxter

  DOI：10.1039/b310443p

  日期：——

  The product of the first transamination step in the reaction catalysed by diaminopelargonate (DAPA) synthase has been shown to be 4-(S-adenosyl)-2-oxobutanoate, which has been trapped as the corresponding alcohol.

  由二氨基佩拉尔戈酸（DAPA）合酶催化的反应中，第一个转氨基化步骤的产物已被证明是4-(S-腺苷)-2-氧代丁酸，该产物已被捕获为相应的醇。