纳二烯合成酶结构和模块化架构的演变在烯生物合成中
Mustafa Köksal1, Yinghua Jin, Robert M Coates
1Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, USA.
Nature
|December 17, 2010
概括
纳税二烯合成酶 (TXS) 的晶体结构显示出混合循环酶结构. 这一发现阐明了不同类型的特类环酶之间的进化联系,这对Taxol生物合成至关重要.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 自然产品生物合成 自然产品生物合成
背景情况:
- 类,包括抗癌药物Taxol,是各种各样的自然产品.
- 纳醇生物合成涉及由纳二烯合成酶 (TXS) 循环转化基兰二酸盐 (GGPP).
- 了解TXS结构是阐明Taxol复杂生物合成途径的关键.
研究的目的:
- 为了确定一个截断的纳税合成酶 (TXS) 变体的X射线晶体结构.
- 调查GGPP循环和Taxol前体形成的结构基础.
- 探索不同类型的特类循环酶之间的进化关系.
主要方法:
- 使用X射线晶体学来确定TXS的结构.
- 解决了TXS与基质类似物复合的结构:13-aza-13,14-dihydrocopalyl二酸盐和2-fluorogeranylgeranyl二酸盐.
- 对三维结构的分析揭示了域组织和催化机械.
主要成果:
- 该TXS结构呈现出一个独特的模块化组装三个alpha-helical领域.
- 该C终端域作为I类特类环酶,利用三金属离子集群进行GGPP激活.
- N终端和"插入"域采用了残留II类特类循环酶的折叠特征.
结论:
- TXS的混合结构为不同的循环类的进化融合提供了直接的证据.
- 这一发现揭示了类生物合成中的机械和进化途径.
- 结构洞察力有助于了解像Taxol.这样有价值的自然产品的生产.
相关概念视频
Structure of Conjugated Dienes
Introduction
Conjugated dienes are compounds characterized by the presence of alternating double and single bonds. In a conjugated system like 1,3-butadiene, the unhybridized 2p orbital on each carbon overlaps continuously, allowing the π electrons to be delocalized across the entire molecule. In contrast, this type of overlap does not occur in cumulated and isolated dienes, such as 2,3-pentadiene and 1,4-pentadiene, respectively. Instead, the π electrons remain localized between the double...
Conjugated dienes are compounds characterized by the presence of alternating double and single bonds. In a conjugated system like 1,3-butadiene, the unhybridized 2p orbital on each carbon overlaps continuously, allowing the π electrons to be delocalized across the entire molecule. In contrast, this type of overlap does not occur in cumulated and isolated dienes, such as 2,3-pentadiene and 1,4-pentadiene, respectively. Instead, the π electrons remain localized between the double...
[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction
The Diels–Alder reaction is an example of a thermal pericyclic reaction between a conjugated diene and an alkene or alkyne, commonly referred to as a dienophile. The reaction involves a concerted movement of six π electrons, four from the diene and two from the dienophile, forming an unsaturated six-membered ring. As a result, these reactions are classified as [4+2] cycloadditions.
Diels–Alder Reaction Forming Cyclic Products: Stereochemistry
The Diels–Alder reaction is one of the robust methods for synthesizing unsaturated six-membered rings. The reaction involves a concerted cyclic movement of six π electrons: four π electrons from the diene and two π electrons from the dienophile.
Diels–Alder Reaction: Characteristics of Dienes
The Diels–Alder reaction brings together a diene and a dienophile to form a six-membered ring. Both components have unique characteristics that influence the rate of the reaction.
Characteristics of the diene
Conformation
The simplest example of a diene is 1,3-butadiene, an acyclic conjugated π system. At room temperature, the molecule exists as a mixture of s-cis and s-trans conformers by virtue of rotation around the carbon–carbon single bond. Although the s-trans isomer is more stable, the...
Characteristics of the diene
Conformation
The simplest example of a diene is 1,3-butadiene, an acyclic conjugated π system. At room temperature, the molecule exists as a mixture of s-cis and s-trans conformers by virtue of rotation around the carbon–carbon single bond. Although the s-trans isomer is more stable, the...
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Acyclic diene metathesis polymerization or ADMET polymerization involves cross-metathesis of terminal dienes, such as 1,8-nonadiene, to give linear unsaturated polymer and ethylene. As ADMET is a reversible process, the formed ethylene gas must be removed from the reaction mixture to complete the polymerization process.
Similar to cross-metathesis, ADMET also involves the formation of metallacyclobutane intermediate by [2+2] cycloaddition of one of the double bonds of a terminal diene with...
Similar to cross-metathesis, ADMET also involves the formation of metallacyclobutane intermediate by [2+2] cycloaddition of one of the double bonds of a terminal diene with...
Diels–Alder Reaction Forming Bridged Bicyclic Products: Stereochemistry
Diels–Alder reactions between cyclic dienes locked in an s-cis configuration and dienophiles yield bridged bicyclic products.


