从更高的真核生物中对费里丁的铁氧化酶位点的结构洞察
Ivano Bertini1, Daniela Lalli, Stefano Mangani
1Magnetic Resonance Center (CERM), University of Florence, 50019 Sesto Fiorentino, Florence, Italy. ivanobertini@cerm.unifi.it
Journal of the American Chemical Society
|March 20, 2012
概括
这项研究揭示了在较高的真核生物铁素中首次结构性识别不同的物种,详细说明了铁氧化酶活性部位的铁和铜离子协调. 这为ferritin提供了关键的见解.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 生物矿物化 生物矿物化
背景情况:
- 费里丁通过其铁氧化酶活性位点的氧化来调解铁的生物矿物化.
- 了解铁氧化过程中的结构中间体对于阐明费里的机制至关重要.
研究的目的:
- 确定金属载荷费里的结构,特别关注铁氧化酶活性部位的不同物种.
- 为了比较铁和铜在费里中添加物的结构特征.
主要方法:
- 采用X射线晶体学,获得浸泡在铁 (FeSO4) 和铜 (CuSO4) 溶液中的青铁素晶体的高分辨率结构.
- 异常差异里埃图被用来识别金属离子位置和协调环境.
主要成果:
- 具有微氧/桥 (Fe-Fe 距离~3.1 Å) 的不同物种的第一个结构证据在更高的真核生物铁素中观察到.
- 铜结合揭示了二铜 (II) 中心,与铁相比,具有明显的协调和增加的金属间距离 (~4.3 Å),涉及His54.
- 快速浸泡实验捕获过渡性二铁物种,支持拟议的催化机制.
结论:
- 已识别的不同物种及其协调为高细胞核中的费里丁的铁氧化机制提供了关键的结构信息.
- 铜的独特结构行为表明,在铁氧化酶位点对双价离子相互作用的特定特征.
- 这些发现有助于进一步了解铁素在铁的吸收,氧化和储存中的作用.
相关概念视频
Conserved Binding Sites
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Ligand Binding and Linkage
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence the...
The Early Endosome: Endocytosis of Transferrin
Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
Gene Families
Gene families consist of groups of genes proposed to have originated from a common ancestor. Typically these arise through events in which a gene or genes are mistakenly duplicated during cell division. Unlike their parent genes (which are subject to selection pressure to maintain function), these gene copies do not need to preserve their sequences and may evolve at a relatively faster rate.
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
Allosteric Proteins-ATCase
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Microbes and Other Elemental Cycles
Microbial activity plays a pivotal role in the biogeochemical cycling of iron and manganese, especially at the redox gradients characteristic of stratified aquatic environments. These cycles are driven by microbial transformations between oxidized and reduced forms of the metals, allowing organisms to exploit them for metabolic energy and structural purposes.Iron Cycling Across Redox GradientsIn neutral, oxygen-rich surface waters, iron is predominantly found in its oxidized, insoluble ferric...


![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)