在单个原子的水平上减少cuproenzyme酸盐的结构基础
Yohta Fukuda1, Masami Lintuluoto2, Yu Hirano3
1Graduate School of Pharmaceutical Science, Osaka University, Suita, Osaka, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Suita, Osaka, Japan.
The Journal of biological chemistry
|May 28, 2025
概括
中子晶体学揭示了含铜的酸盐还原酶 (CuNIRs) 如何结合酸盐并启动催化. 这项研究澄清了酶.
科学领域:
- 生物化学和结构生物学.
- 酶学 是一种酶学.
- 生物物理化学 生物物理化学
背景情况:
- 原子对于生物宏分子功能至关重要,包括酶活性.
- 含铜酸还原酶 (CuNIRs) 是参与循环的重要酶,具有医学和环境影响.
- 在CuNIRs中,精确的催化机制和原子动态仍然不太清楚.
研究的目的:
- 阐明CuNIR催化机制的初始步骤.
- 为了确定酸盐的结合方式和催化残留的作用.
- 了解CuNIR酶反应期间的原子动态.
主要方法:
- 中子晶体学用于H原子分辨率结构的确定.
- 野生类型和突变酶的亚原子分辨率结构的X射线晶体学.
- 量子化学计算以支持结构和机制解释.
主要成果:
- 化物以NO2的形式与催化铜中心结合,而不是以质子化HNO2的形式结合.
- 催化残留物HisCAT是质子化,而AspCAT是脱质子化,表明HisCAT启动了质子转移.
- 酶的活性部位表现出由溶剂分子稳定的电子局部状态.
- 突变研究表明,质子化AspCAT对于初始反应步骤并不重要.
结论:
- 该研究揭示了CuNIR催化机制的详细第一步.
- 中子晶体学为酶反应中的H原子位置提供了前所未有的洞察力.
- 这些发现有助于进一步了解CuNIR功能和代谢.
相关概念视频
Preparation of Amines: Reduction of Oximes and Nitro Compounds
4.1K
Oximes can be reduced to primary amines using catalytic hydrogenation, hydride reduction, or sodium metal reduction. The reduction of aliphatic and aromatic nitro compounds to primary amines takes place by either catalytic hydrogenation or by using active metals like Fe, Zn, and Sn in the presence of an acid.
Though catalytic hydrogenation can reduce nitrobenzenes, the reduction is nonselective in the presence of other functional groups. For instance, if nitrobenzene contains an aldehyde group,...
Though catalytic hydrogenation can reduce nitrobenzenes, the reduction is nonselective in the presence of other functional groups. For instance, if nitrobenzene contains an aldehyde group,...
4.1K
Oxidation and Reduction of Organic Molecules
7.8K
Energy production within a cell involves many coordinated chemical pathways. Most of these pathways are combinations of oxidation and reduction reactions, which occur at the same time. An oxidation reaction strips an electron from an atom in a compound, and the addition of this electron to another compound is a reduction reaction. Because oxidation and reduction usually occur together, these pairs of reactions are called redox reactions.
The removal of an electron from a molecule, results in a...
The removal of an electron from a molecule, results in a...
7.8K
Role of Reduced Coenzymes NADH and FADH₂
12.7K
The energy released from the breakdown of the chemical bonds within nutrients can be stored either through the reduction of electron carriers or in the bonds of adenosine triphosphate (ATP). In living systems, a small class of compounds functions as mobile electron carriers, molecules that bind to and shuttle high-energy electrons between compounds in pathways. The principal electron carriers that will be considered originate from the B vitamin group and are derivatives of nucleotides; they are...
12.7K
Reduction of Alkenes: Asymmetric Catalytic Hydrogenation
3.4K
Catalytic hydrogenation of alkenes is a transition-metal catalyzed reduction of the double bond using molecular hydrogen to give alkanes. The mode of hydrogen addition follows syn stereochemistry.
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
3.4K
Electrophilic Aromatic Substitution: Nitration of Benzene
6.6K
The nitration of benzene is an example of an electrophilic aromatic substitution reaction. It involves the formation of a very powerful electrophile, the nitronium ion, which is linear in shape. The reaction occurs through the interaction of two strong acids, sulfuric and nitric acid.
6.6K
Nitriles to Amines: LiAlH4 Reduction
3.8K
Nitriles are reduced to amines in the presence of strong reducing agents like lithium aluminum hydride through a typical nucleophilic acyl substitution. The reaction requires two equivalents of the reducing agent. The reducing agent acts as a source of hydride ions.
As shown below, the mechanism involves three steps. Firstly, the hydride ion acting as a nucleophile attacks the nitrile carbon to form an anion. In the second step, a second equivalent of the hydride ion attacks the anion to...
As shown below, the mechanism involves three steps. Firstly, the hydride ion acting as a nucleophile attacks the nitrile carbon to form an anion. In the second step, a second equivalent of the hydride ion attacks the anion to...
3.8K
![Protein Film Infrared Electrochemistry Demonstrated for Study of H2 Oxidation by a [NiFe] Hydrogenase](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F55858.jpg&w=3840&q=50)

