三羧酸循环超配合物静电通道的马尔可夫状态研究

IF 4.8 Q2 NANOSCIENCE & NANOTECHNOLOGY ACS Nanoscience Au Pub Date : 2022-06-07 DOI:10.1021/acsnanoscienceau.2c00011
Yan Xie, Shelley D. Minteer, Scott Banta and Scott Calabrese Barton*, 
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引用次数: 0

摘要

超分子酶纳米组件中高效的级联反应,被称为代谢,已经引起了各个领域的广泛关注,从基础生物化学和分子生物学到最近在生物燃料电池、生物传感器和化学合成中的应用。代谢效率高的一个原因是由顺序酶形成的结构允许在连续活性位点之间直接运输中间体。苹果酸脱氢酶(MDH)和柠檬酸合成酶(CS)的超络合物是通过静电通道控制中间体运输的理想例子。本文采用分子动力学(MD)模拟和马尔可夫状态模型(MSM)相结合的方法,研究了中间体草酰乙酸(OAA)从MDH到CS的转运过程。MSM能够确定OAA从MDH到CS的主要运输途径。使用枢纽评分方法对所有途径进行分析,揭示了控制OAA运输的一小部分残基。这一组包括精氨酸残基先前的实验鉴定。MSM分析一个突变复合体,其中鉴定的精氨酸被丙氨酸取代,导致转移效率降低2倍,也与实验结果一致。这项工作提供了对静电通道机制的分子水平的理解,并将使利用静电通道的催化纳米结构的进一步设计成为可能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Markov State Study of Electrostatic Channeling within the Tricarboxylic Acid Cycle Supercomplex

The high efficiency of cascade reactions in supramolecular enzyme nanoassemblies, known as metabolons, has attracted substantial attention in various fields ranging from fundamental biochemistry and molecular biology to recent applications in biofuel cells, biosensors, and chemical synthesis. One reason for the high efficiency of metabolons is the structures formed by sequential enzymes that allow the direct transport of intermediates between consecutive active sites. The supercomplex of malate dehydrogenase (MDH) and citrate synthase (CS) is an ideal example of the controlled transport of intermediates via electrostatic channeling. Here, using a combination of molecular dynamics (MD) simulations and a Markov state model (MSM), we examined the transport process of the intermediate oxaloacetate (OAA) from MDH to CS. The MSM enables the identification of the dominant transport pathways of OAA from MDH to CS. Analysis of all pathways using a hub score approach reveals a small set of residues that control OAA transport. This set includes an arginine residue previously identified experimentally. MSM analysis of a mutated complex, where the identified arginine is replaced by alanine, led to a 2-fold decrease in transfer efficiency, also consistent with experimental results. This work provides a molecular-level understanding of the electrostatic channeling mechanism and will enable the further design of catalytic nanostructures utilizing electrostatic channeling.

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来源期刊
ACS Nanoscience Au
ACS Nanoscience Au 材料科学、纳米科学-
CiteScore
4.20
自引率
0.00%
发文量
0
期刊介绍: ACS Nanoscience Au is an open access journal that publishes original fundamental and applied research on nanoscience and nanotechnology research at the interfaces of chemistry biology medicine materials science physics and engineering.The journal publishes short letters comprehensive articles reviews and perspectives on all aspects of nanoscience and nanotechnology:synthesis assembly characterization theory modeling and simulation of nanostructures nanomaterials and nanoscale devicesdesign fabrication and applications of organic inorganic polymer hybrid and biological nanostructuresexperimental and theoretical studies of nanoscale chemical physical and biological phenomenamethods and tools for nanoscience and nanotechnologyself- and directed-assemblyzero- one- and two-dimensional materialsnanostructures and nano-engineered devices with advanced performancenanobiotechnologynanomedicine and nanotoxicologyACS Nanoscience Au also publishes original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials engineering physics bioscience and chemistry into important applications of nanomaterials.
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