Vinorine

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 可吗灵-沙巴秦生物碱
• 英文名称: Vinorine
• 英文别名: [(1R,10S,12R,13E,16S,18R)-13-ethylidene-8,15-diazahexacyclo[14.2.1.01,9.02,7.010,15.012,17]nonadeca-2,4,6,8-tetraen-18-yl] acetate
• 化学式: C₂₁H₂₂N₂O₂
• 分子量: 334.4
• InChiKey: CLDVMRAEPFQOSD-WEOXKLFPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  41.9
• 氢给体数：
  0
• 氢受体数：
  4

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	16-epi-vellosimine	88199-28-4	C19H20N2O	292.381

反应信息

• 作为反应物：
  描述：

  氧气 、 1-Deoxy-1-(7,8-dimethyl-2,4-dioxidobenzo[g]pteridin-10(5H)-yl)-5-O-phosphonopentitol 、 Vinorine 生成 氢(+1)阳离子 、 水 、 FMN 、 vomilenine
  参考文献：
  名称：

  摘要：

  DOI：
• 作为产物：
  描述：

  16-epi-vellosimine 、 (2R)-N-[3-(2-acetylsulfanylethylimino)-3-oxidopropyl]-4-[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonatooxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-2-hydroxy-3,3-dimethylbutanimidate 生成 coenzyme A 、 Vinorine
  参考文献：
  名称：

  Acetyltransfer in natural product biosynthesis––functional cloning and molecular analysis of vinorine synthase

  摘要：

  Vinorine synthase (EC 2.3.1.160) catalyses the acetyl-CoA- or CoA-dependent reversible formation of the alkaloids vinorine (or 11-methoxy-vinorine) and 16-epi-vellosimine (or gardneral). The forward reaction leads to vinorine, which is a direct biosynthetic precursor along the complex pathway to the monoterpenoid indole alkaloid ajmaline, an antiarrhythmic drug from the Indian medicinal plant Rauvolfia serpentina. Based on partial peptide sequences a cDNA clone was isolated and functionally expressed in Escherichia coli. The K-m values of the native enzyme for gardneral and acetyl-CoA were determined to be 7.5 and 57 muM. The amino acid sequence of vinorine synthase has highest level of identity (28-31%) to that of Papaver salutaridinol acetyltransferase. Fragaria alcohol acyltransferase, and Catharanthus deacetylvindoline acetyltransferase involved in morphine, flavor, and vindoline biosynthesis, respectively. Vinorine synthase is a novel member of the BAHD superfamily of acyltransferases. Site-directed mutagenesis of 13 amino acid residues provided clear evidence that both, His160 and Asp164 of the consensus sequence HxxxD belong to the catalytic center. The Mutations also showed that an amino acid triad is not characteristic of vinorine synthase. The experiments demonstrated the importance of the conserved motif SxL/I/VD near the N-terminus and the consensus sequence DFGWG near the C-terminal. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.02.029

文献信息

• Acetyltransfer in natural product biosynthesis––functional cloning and molecular analysis of vinorine synthase
  作者：Anja Bayer、Xueyan Ma、Joachim Stöckigt

  DOI：10.1016/j.bmc.2004.02.029

  日期：2004.5

  Vinorine synthase (EC 2.3.1.160) catalyses the acetyl-CoA- or CoA-dependent reversible formation of the alkaloids vinorine (or 11-methoxy-vinorine) and 16-epi-vellosimine (or gardneral). The forward reaction leads to vinorine, which is a direct biosynthetic precursor along the complex pathway to the monoterpenoid indole alkaloid ajmaline, an antiarrhythmic drug from the Indian medicinal plant Rauvolfia serpentina. Based on partial peptide sequences a cDNA clone was isolated and functionally expressed in Escherichia coli. The K-m values of the native enzyme for gardneral and acetyl-CoA were determined to be 7.5 and 57 muM. The amino acid sequence of vinorine synthase has highest level of identity (28-31%) to that of Papaver salutaridinol acetyltransferase. Fragaria alcohol acyltransferase, and Catharanthus deacetylvindoline acetyltransferase involved in morphine, flavor, and vindoline biosynthesis, respectively. Vinorine synthase is a novel member of the BAHD superfamily of acyltransferases. Site-directed mutagenesis of 13 amino acid residues provided clear evidence that both, His160 and Asp164 of the consensus sequence HxxxD belong to the catalytic center. The Mutations also showed that an amino acid triad is not characteristic of vinorine synthase. The experiments demonstrated the importance of the conserved motif SxL/I/VD near the N-terminus and the consensus sequence DFGWG near the C-terminal. (C) 2004 Elsevier Ltd. All rights reserved.
• Vinorine synthase from Rauvolfia: the first example of crystallization and preliminary X-ray diffraction analysis of an enzyme of the BAHD superfamily
  作者：Xueyan Ma、Juergen Koepke、Anja Bayer、Verena Linhard、Günter Fritzsch、Bin Zhang、Hartmut Michel、Joachim Stöckigt

  DOI：10.1016/j.bbapap.2004.06.011

  日期：2004.9

  Crystals of vinorine synthase (VS) from medicinal plant Rauvolfia serpentina expressed in Escherichia coli have been obtained by the hanging-drop technique at 305 K with ammonium sulfate and PEG 400 as precipitants. The enzyme is involved in the biosynthesis of the antiarrhythmic drug ajmaline and is a member of the BAHD superfamily of acyltransferases. So far, no three-dimensional structure of a member of this enzyme family is known. The crystals belong to the space group P2(1)2(1)2(1) with cell dimensions of a=82.3 Angstrom, b=89.6 Angstrom and c=136.2 Angstrom. Under cryoconditions (120 K), a complete data set up to 2.8 Angstrom was collected at a synchrotron source. (C) 2004 Elsevier B.V. All rights reserved.
• Crystal Structure of Vinorine Synthase, the First Representative of the BAHD Superfamily
  作者：Xueyan Ma、Juergen Koepke、Santosh Panjikar、Günter Fritzsch、Joachim Stöckigt

  DOI：10.1074/jbc.m414508200

  日期：2005.4

  Vinorine synthase is an acetyltransferase that occupies a central role in the biosynthesis of the antiarrhythmic monoterpenoid indole alkaloid ajmaline in the plant Rauvolfia. Vinorine synthase belongs to the benzylalcohol acetyl-, anthocyanin-O-hydroxy-cinnamoyl-, anthranilate-N-hydroxy-cinnamoyl/benzoyl-, deacetylvindoline acetyltransferase (BAHD) enzyme superfamily, members of which are involved in the biosynthesis of several important drugs, such as morphine, Taxol, or vindoline, a precursor of the anti-cancer drugs vincaleucoblastine and vincristine. The x-ray structure of vinorine synthase is described at 2.6-angstrom resolution. Despite low sequence identity, the two-domain structure of vinorine synthase shows surprising similarity with structures of several CoA-dependent acyltransferases such as dihydrolipoyl transacetylase, polyketide-associated protein A5, and carnitine acetyltransferase. All conserved residues typical for the BAHD family are found in domain 1. His160 of the HXXXD motif functions as a general base during catalysis. It is located in the center of the reaction channel at the interface of both domains and is accessible from both sides. The channel runs through the entire molecule, allowing the substrate and co-substrate to bind independently. Asp164 points away from the catalytic site and seems to be of structural rather than catalytic importance. Surprisingly, the DFGWG motif, which is indispensable for the catalyzed reaction and unique to the BAHD family, is located far away from the active site and seems to play only a structural role. Vinorine synthase represents the first solved protein structure of the BAHD superfamily.