pyridine-2-carboxyloyl-CoA | 404355-22-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: pyridine-2-carboxyloyl-CoA
• 英文别名: S-[2-[3-[[(2R)-4-[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-2-hydroxy-3,3-dimethylbutanoyl]amino]propanoylamino]ethyl] pyridine-2-carbothioate
• CAS: 404355-22-2
• 化学式: C₂₇H₃₉N₈O₁₇P₃S
• 分子量: 872.637
• InChiKey: ZLHFOSYHYYRVMC-MJQNIGQHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.7
• 重原子数：
  56
• 可旋转键数：
  21
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  402
• 氢给体数：
  9
• 氢受体数：
  23

反应信息

• 作为反应物：
  描述：

  3-氧代癸酸 、 pyridine-2-carboxyloyl-CoA 、 丙二酰辅酶A-钠盐 在 Huperzia serrata type III polyketide synthase 作用下， 以 aq. phosphate buffer 、 二甲基亚砜 为溶剂， 反应 12.0h， 生成
  参考文献：
  名称：

  Synthesis of Unnatural 2-Substituted Quinolones and 1,3-Diketones by a Member of Type III Polyketide Synthases from Huperzia serrata

  摘要：

  A curcuminoids, benzalacetone-, and quinolone-producing type III polyketide synthase (HsPKS3) from Huperzia serrata uniquely catalyzes the formation of unnatural 2-substituted quinolones and 1,3-diketones via head-to-head condensation of two completely different substrates. The broad range of substrate tolerance of HsPKS3 facilitates accessing structurally diverse 2-substituted quinolones and 1,3-diketones.

  DOI：

  10.1021/acs.orglett.6b01501
• 作为产物：
  描述：

  2-吡啶甲酸 在 氯化亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 aq. phosphate buffer 、 二氯甲烷 为溶剂， 生成 pyridine-2-carboxyloyl-CoA
  参考文献：
  名称：

  组合化学在抗霉素生物合成中的复用：分子多样性和实用性的扩展

  摘要：

  通过使用多重组合生物合成，完成了抗霉素样化合物库（共380个）的面向多样性的生物合成。核心策略取决于在不同生物合成阶段使用组合化学。该方法适用于聚酮化合物，非核糖体肽以及具有相似生物合成逻辑的杂种的多样化。

  DOI：

  10.1002/anie.201305569

文献信息

• Substrate Specificity, Substrate Channeling, and Allostery in BphJ: An Acylating Aldehyde Dehydrogenase Associated with the Pyruvate Aldolase BphI
  作者：Perrin Baker、Jason Carere、Stephen Y. K. Seah

  DOI：10.1021/bi300407y

  日期：2012.6.5

  BphJ, a nonphosphorylating acylating aldehyde dehydrogenase, catalyzes the conversion of aldehydes to form acyl-coenzyme A in the presence of NAD(+) and coenzyme A (CoA). The enzyme is structurally related to the nonacylating aldehyde dehydrogenases, aspartate-β-semialdehyde dehydrogenase and phosphorylating glyceraldehyde-3-phosphate dehydrogenase. Cys-131 was identified as the catalytic thiol in BphJ, and pH profiles together with site-specific mutagenesis data demonstrated that the catalytic thiol is not activated by an aspartate residue, as previously proposed. In contrast to the wild-type enzyme that had similar specificities for two- or three-carbon aldehydes, an I195A variant was observed to have a 20-fold higher catalytic efficiency for butyraldehyde and pentaldehyde compared to the catalytic efficiency of the wild type toward its natural substrate, acetaldehyde. BphJ forms a heterotetrameric complex with the class II aldolase BphI that channels aldehydes produced in the aldol cleavage reaction to the dehydrogenase via a molecular tunnel. Replacement of Ile-171 and Ile-195 with bulkier amino acid residues resulted in no more than a 35% reduction in acetaldehyde channeling efficiency, showing that these residues are not critical in gating the exit of the channel. Likewise, the replacement of Asn-170 in BphJ with alanine and aspartate did not substantially alter aldehyde channeling efficiencies. Levels of activation of BphI by BphJ N170A, N170D, and I171A were reduced by ≥3-fold in the presence of NADH and ≥4.5-fold when BphJ was undergoing turnover, indicating that allosteric activation of the aldolase has been compromised in these variants. The results demonstrate that the dehydrogenase coordinates the catalytic activity of BphI through allostery rather than through aldehyde channeling.