(1R,2R,4S)-2-ethyl-2,7-dihydroxy-1-(methoxycarbonyl)-6,11-dioxo-4-{[2,3,6-trideoxy-4-O-{2,6-dideoxy-4-O-[(2S,5S,6S)-5-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]-alpha-L-lyxo-hexopyranosyl}-3-(dimethylammonio)-alpha-L-lyxo-hexopyranosyl]oxy}-1,2,3,4,6,11-hexahydrotetracen-5-olate | 64474-88-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 蒽环类药物
• 英文名称: (1R,2R,4S)-2-ethyl-2,7-dihydroxy-1-(methoxycarbonyl)-6,11-dioxo-4-{[2,3,6-trideoxy-4-O-{2,6-dideoxy-4-O-[(2S,5S,6S)-5-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]-alpha-L-lyxo-hexopyranosyl}-3-(dimethylammonio)-alpha-L-lyxo-hexopyranosyl]oxy}-1,2,3,4,6,11-hexahydrotetracen-5-olate
• 英文别名: (1R,2R,4S)-4-[(2R,4S,5S,6S)-4-(dimethylazaniumyl)-5-[(2S,4S,5S,6S)-4-hydroxy-5-[(2S,5S,6S)-5-hydroxy-6-methyloxan-2-yl]oxy-6-methyloxan-2-yl]oxy-6-methyloxan-2-yl]oxy-2-ethyl-2,7-dihydroxy-1-methoxycarbonyl-6,11-dioxo-3,4-dihydro-1H-tetracen-5-olate
• CAS: 64474-88-0
• 化学式: C42H55NO15
• 分子量: 813.9
• InChiKey: CPUWOKRFRYWIHK-BPPBZOKFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  58
• 可旋转键数：
  10
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  220
• 氢给体数：
  5
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  (1R,2R,4S)-2-ethyl-2,7-dihydroxy-1-(methoxycarbonyl)-6,11-dioxo-4-{[2,3,6-trideoxy-4-O-{2,6-dideoxy-4-O-[(2S,5S,6S)-5-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]-alpha-L-lyxo-hexopyranosyl}-3-(dimethylammonio)-alpha-L-lyxo-hexopyranosyl]oxy}-1,2,3,4,6,11-hexahydrotetracen-5-olate 、 氧气 生成 阿克拉霉素 、 双氧水
  参考文献：
  名称：

  来自抗生素阿克拉霉素的生物合成途径的阿克拉霉素氧化还原酶（AknOx）是一种具有双重活性位点的不常见的黄素酶。

  摘要：

  Aclacinomycin（Acl）氧化还原酶（AknOx）催化Acl组聚酮化合物抗生素生物合成中的最后两个步骤，即将末端糖部分的若丹糖氧化为l-琼脂糖。我们介绍了结合有FAD的AknOx的晶体结构和精炼至1.65-A分辨率的产品AclY。AknOx的整体折叠将酶鉴定为对甲酚甲基羟化酶超家族的成员。辅助因子以8alpha-Ndelta1-histidyl，6-S-cysteinyl FAD双价共价结合到His-70和Cys-130上。聚酮化合物配体在底物结合结构域的深裂缝中结合，四环系统靠近酶表面，三糖链延伸到蛋白质内部。末端糖残基堆积在FAD的异四嗪环上，并将被氧化的碳原子置于FAD的N5原子附近。此处呈现的结构和定点诱变数据与一种机制相吻合，在该机制中，AknOx的两种不同反应在相同的活性位点被不同的活性位点残基催化。Tyr-450负责在第一个反应中从C-4羟基中除去质子，将罗丹糖氧化

  DOI：

  10.1073/pnas.0700579104

文献信息

• Aclacinomycin oxidoreductase (AknOx) from the biosynthetic pathway of the antibiotic aclacinomycin is an unusual flavoenzyme with a dual active site
  作者：Igor Alexeev、Azmiri Sultana、Pekka Mäntsälä、Jarmo Niemi、Gunter Schneider

  DOI：10.1073/pnas.0700579104

  日期：2007.4.10

  domain, with the tetracyclic ring system close to the enzyme surface and the three-sugar chain extending into the protein interior. The terminal sugar residue packs against the isoalloxazine ring of FAD and positions the carbon atoms that are oxidized close to the N5 atom of FAD. The structure and site-directed mutagenesis data presented here are consistent with a mechanism where the two different reactions

  Aclacinomycin（Acl）氧化还原酶（AknOx）催化Acl组聚酮化合物抗生素生物合成中的最后两个步骤，即将末端糖部分的若丹糖氧化为l-琼脂糖。我们介绍了结合有FAD的AknOx的晶体结构和精炼至1.65-A分辨率的产品AclY。AknOx的整体折叠将酶鉴定为对甲酚甲基羟化酶超家族的成员。辅助因子以8alpha-Ndelta1-histidyl，6-S-cysteinyl FAD双价共价结合到His-70和Cys-130上。聚酮化合物配体在底物结合结构域的深裂缝中结合，四环系统靠近酶表面，三糖链延伸到蛋白质内部。末端糖残基堆积在FAD的异四嗪环上，并将被氧化的碳原子置于FAD的N5原子附近。此处呈现的结构和定点诱变数据与一种机制相吻合，在该机制中，AknOx的两种不同反应在相同的活性位点被不同的活性位点残基催化。Tyr-450负责在第一个反应中从C-4羟基中除去质子，将罗丹糖氧化
• Structure determination by multiwavelength anomalous diffraction of aclacinomycin oxidoreductase: indications of multidomain pseudomerohedral twinning
  作者：Azmiri Sultana、Igor Alexeev、Inari Kursula、Pekka Mäntsälä、Jarmo Niemi、Gunter Schneider

  DOI：10.1107/s0907444906044271

  日期：2007.2.1

  The crystal structure of aclacinomycin oxidoreductase (AknOx), a tailoring enzyme involved in the biosynthesis of the polyketide antibiotic aclacinomycin, was determined to 1.65 A resolution by multiwavelength anomalous diffraction using data from selenomethionine-substituted crystals. The crystals belong to space group P2(1), with unit-cell parameters a = 68.2, b = 264.5, c = 68.2 A, beta = 119 degrees . Analysis of the intensity statistics clearly showed the presence of pseudomerohedral twinning. The data set could also be indexed and scaled with an R(sym) of 0.072 in the orthorhombic space group C222(1) (unit-cell parameters a = 69.7, b = 117.5, c = 264.4 A), indicating the possibility of pseudomerohedral twinning along the diagonal between the monoclinic a and c directions. Refinement using this twin operator resulted in an R(free) of 24.2%. A monoclinic lattice with a = c and beta close to 120 degrees can emulate a hexagonal metric, with the possibility of a threefold twin operator along the b axis and three twin domains. Refinement assuming three-domain twinning gave a final R(free) of 26.5%. The structure of AknOx can be thus refined with comparable R(free) values using either of the twin operators separately, suggesting the possibility that crystals of AknOx contain six twin domains generated by the twofold and threefold twin operators perpendicular to each other. Both twin operators coincide with noncrystallographic symmetry axes that may promote twinning.