表面因子合成酶的外部 thioesterase 的选择性的结构基础
Alexander Koglin1, Frank Löhr, Frank Bernhard
1Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance and Cluster of Excellence Macromolecular Complexes (CEF), J.W.-Goethe University, 60438 Frankfurt am Main, Germany.
Nature
|August 16, 2008
概括
二型二氧化酶 (TEII) 是非核糖体和多基合成酶的关键修复酶. 结构分析揭示了TEII酶如何再生功能辅因子,使其与I型硫酶 (TEI) 不同.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- 非核糖体合成酶 (NRPS) 和多基合成酶 (PKS) 对于各种生物体中产生生物活性化合物至关重要.
- 这些系统利用I型化酶 (TEI) 进行产品释放,并使用II型化酶 (TEII) 进行辅助因子修复.
- TEII酶对于在化 (T) 域上再生4'-酸 (4'-PP) 辅因子至关重要,防止生物合成途径中断.
研究的目的:
- 为了阐明一种来自 Bacillus subtilis 的II型硫酶 (TEII) 的三维结构.
- 为了比较TEII和TEI酶之间的基质选择性和域相互作用的结构基础.
- 为了研究TEII与其基板相关的结构动态.
主要方法:
- 使用X射线晶体学来确定Bacillus subtilis TEII的结构,无论是在自由状态还是与T域相结合.
- 在TEII和已知的TEI结构之间进行了比较结构分析.
- 生物化学试验被用来研究TEII酶构造和基质相互作用.
主要成果:
- 该研究报告了细菌TEII酶的高分辨率三维结构及其具有T域的复合体.
- 结构性比较突出了TEII和TEI酶之间基质选择性和T域相互作用的独特机制.
- 证明TEII存在多种构造,基质结合诱导特定的构造选择.
结论:
- 结构洞察力为NRPS和PKS途径中的辅因子再生中的TEII功能提供了分子理解.
- 这些发现澄清了TEI和TEII酶之间的差异,这对于理解二次代谢物生物合成至关重要.
- 形状选择机制突出了TEII-基质相互作用的特异性,这对于保持这些复杂的生物合成机械的完整性至关重要.
相关概念视频
Surface Active Agents
Surfactants, named for their behavior at interfaces, positively adsorb at the interfaces of two phases, reducing interfacial tension. Their versatility as emulsifiers, detergents, and foaming agents stems from this ability. Surfactants, often termed amphiphiles, share the property of amphipathy, with molecules having both hydrophilic and hydrophobic portions. The hydrophilic part is called the head, and the hydrophobic part, including an elongated alkyl substituent, forms the tail.Surfactants...
Tail-anchoring of Proteins in the ER Membrane
Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
Preparation and Reactions of Thiols
Thiols are prepared using the hydrosulfide anion as a nucleophile in a nucleophilic substitution reaction with alkyl halides. For instance, bromobutane reacts with sodium hydrosulfide to give butanethiol.
Induced-fit Model
Most chemical reactions in cells require enzymes—biological catalysts that speed up the reaction without being consumed or permanently changed. They reduce the activation energy needed to convert the reactants into products. Enzymes are proteins, that usually work by binding to a substrate—a reactant molecule that they act upon.
Enzymes exhibit substrate specificity, meaning that they can only bind to certain substrates. This is mainly determined by the shape and chemical characteristics of...
Enzymes exhibit substrate specificity, meaning that they can only bind to certain substrates. This is mainly determined by the shape and chemical characteristics of...
Preparation and Reactions of Sulfides
Sulfides are the sulfur analog of ethers, just as thiols are the sulfur analog of alcohol. Like ethers, sulfides also consist of two hydrocarbon groups bonded to the central sulfur atom. Depending upon the type of groups present, sulfides can be symmetrical or asymmetrical. Symmetrical sulfides can be prepared via an SN2 reaction between 2 equivalents of an alkyl halide and one equivalent of sodium sulfide.
tRNA Activation
Aminoacyl-tRNA synthetases are present in both eukaryotes and bacteria. Though eukaryotes have 20 different aminoacyl-tRNA synthetases to couple to 20 amino acids, many bacteria do not have genes for all of these aminoacyl-tRNA synthetases. Despite this, they still use all 20 amino acids to synthesize their proteins. For instance, some bacteria do not have the gene encoding the enzyme that couples glutamine with its partner tRNA. In these organisms, one enzyme adds glutamic acid to all of the...


