Enzymatic metabolons dramatically enhance metabolic fluxes of low-efficiency biochemical reactions.
Enzymatic metabolons dramatically enhance metabolic fluxes of low-efficiency biochemical reactions.
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酶代谢显着增强低效生化反应的代谢通量。
DOI：
10.1016/j.bpj.2023.10.033
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发表时间：
2023
影响因子：
3.4
通讯作者：
Shakhnovich,Eugene
中科院分区：
文献类型：
--
作者：
Ranganathan,Srivastav;Liu,Junlang;Shakhnovich,Eugene
在这项工作中，我们调查如何空间接近的酶属于同一途径（代谢）影响代谢通量。使用非格点Langevin动力学模拟与随机反应扩散协议和半分析反应扩散模型，我们系统地探讨了蛋白质-蛋白质相互作用，催化效率和蛋白质-配体相互作用的强度如何影响通过代谢子的代谢通量。代谢子的形成导致更长途径的更大加速，特别是对于反应限制的酶，而对于完全优化的扩散限制的酶，效果可以忽略不计。值得注意的是，特定的集群架构不是提高反应通量的先决条件。模拟揭示了最佳非特异性蛋白质-配体相互作用在提高代谢子催化效率中的关键作用。我们的理论意味着，生物信息学分析证实，较长的催化途径富含不太理想的酶，而大多数扩散限制的酶填充较短的途径。我们的研究结果指向一个合理的进化策略，即酶通过增加其在聚集状态下的局部浓度来补偿低于最佳效率。
In this work, we investigate how spatial proximity of enzymes belonging to the same pathway (metabolon) affects metabolic flux. Using off-lattice Langevin dynamics simulations in tandem with a stochastic reaction-diffusion protocol and a semi-analytical reaction-diffusion model, we systematically explored how strength of protein-protein interactions, catalytic efficiency, and protein-ligand interactions affect metabolic flux through the metabolon. Formation of a metabolon leads to a greater speedup for longer pathways and especially for reaction-limited enzymes, whereas, for fully optimized diffusion-limited enzymes, the effect is negligible. Notably, specific cluster architectures are not a prerequisite for enhancing reaction flux. Simulations uncover the crucial role of optimal nonspecific protein-ligand interactions in enhancing catalytic efficiency of a metabolon. Our theory implies, and bioinformatics analysis confirms, that longer catalytic pathways are enriched in less optimal enzymes, whereas most diffusion-limited enzymes populate shorter pathways. Our findings point toward a plausible evolutionary strategy where enzymes compensate for less-than-optimal efficiency by increasing their local concentration in the clustered state.