由烟草5-epi-aristolochene合成酶进行循环烯生物合成的结构基础
C M Starks1, K Back, J Chappell
1Structural Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Science (New York, N.Y.)
|September 20, 1997
概括
烯循环酶合成周期性烯. 晶体结构揭示了5-epi-aristolochene合成酶的意想不到的机制,有助于设计新的烯循环酶.
科学领域:
- 酶学 是一种酶学.
- 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:
- 烯循环酶是从非循环异二酸盐前体合成循环烯的酶.
- 植物是多种类型的烯合成酶的丰富来源,这些酶同类于烯循环酶.
- 循环烯是药理学上重要的天然产品.
研究的目的:
- 为了阐明5-epi-aristolochene合成酶的酶机制,这是来自烟草的基烯环酶.
- 了解环酶生物合成中的立体化学选择性的结构基础.
- 为工程新型烯循环提供结构模板.
主要方法:
- 对5-epi-aristolochene合成酶的晶体结构的分析.
- 与法纳西二酸盐类似物共同结晶.
- 一个X射线晶体学.
主要成果:
- 晶体结构揭示了一种意想不到的酶机制,用于合成双循环产品5-epi-aristolochene.
- 这些结构提供了对烯循环所施加的立体化学控制的见解.
- 分析的结构可以作为酶工程的模板.
结论:
- 这项研究揭示了循环烯生物合成的新机制.
- 了解旋酶结构-功能关系对于药物发现和酶工程至关重要.
- 结构洞察力为设计定制的烯合成酶铺平了道路.
相关概念视频
03:00Preparation of Epoxides
Overview
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy acids to...
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy acids to...
01:26Thermal and Photochemical Electrocyclic Reactions: Overview
Electrocyclic reactions are reversible reactions. They involve an intramolecular cyclization or ring-opening of a conjugated polyene. Shown below are two examples of electrocyclic reactions. In the first reaction, the formation of the cyclic product is favored. In contrast, in the second reaction, ring-opening is favored due to the high ring strain associated with cyclobutene formation.
01:17Thermal Electrocyclic Reactions: Stereochemistry
The stereochemistry of electrocyclic reactions is strongly influenced by the orbital symmetry of the polyene HOMO. Under thermal conditions, the reaction proceeds via the ground-state HOMO.
Selection Rules: Thermal Activation
Conjugated systems containing an even number of π-electron pairs undergo a conrotatory ring closure. For example, thermal electrocyclization of (2E,4E)-2,4-hexadiene, a conjugated diene containing two π-electron pairs, gives trans-3,4-dimethylcyclobutene.
Selection Rules: Thermal Activation
Conjugated systems containing an even number of π-electron pairs undergo a conrotatory ring closure. For example, thermal electrocyclization of (2E,4E)-2,4-hexadiene, a conjugated diene containing two π-electron pairs, gives trans-3,4-dimethylcyclobutene.
01:26Photochemical Electrocyclic Reactions: Stereochemistry
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Selection Rules: Photochemical Activation
Selection Rules: Photochemical Activation
01:28Diels–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.
01:18Aromatic Hydrocarbon Cations: Structural Overview
Cycloheptatriene is a neutral monocyclic unsaturated hydrocarbon that consists of an odd number of carbon atoms and an intervening sp3 carbon in the ring. The three double bonds in the ring correspond to 6 π electrons, which is a Huckel number, and therefore satisfies the criteria of 4n + 2 π electrons. However, the intervening sp3 carbon disrupts the continuous overlap of p orbitals. As a result, cycloheptatriene is not aromatic.
Removing one hydrogen from the intervening CH2 group with both...
Removing one hydrogen from the intervening CH2 group with both...