代谢相互作用的遗传景观
Thuy N Nguyen1,2,3, Christine Ingle1,2,3, Samuel Thompson4
1The Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, USA, 75390.
bioRxiv : the preprint server for biology
|August 30, 2023
概括
细胞代谢需要酶来维持流量并最大限度地减少有害的中间体. 这项研究量化了酶活性变异如何限制代谢酶序列,揭示了对酶进化和系统设计的洞察力.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 系统生物学 系统生物学
背景情况:
- 细胞代谢依赖酶效率来维持流量并防止中间积累.
- 之前的研究集中在蛋白质与蛋白质相互作用上,不清楚代谢功能相互作用的序列约束.
研究的目的:
- 量化一个酶的活动的变化如何限制一个合作伙伴酶的生物化学参数和序列.
- 研究代谢功能相互作用中的序列级约束.
主要方法:
- 聚焦在叶酸代谢中的二叶酸还原酶 (DHFR) 和硫基酸合成酶 (TYMS).
- 采用深度突变扫描来评估3个TYMS背景中的2696个DHFR单个突变.
- 利用了旨在突出生化表观症的条件.
主要成果:
- 开发了一种将酶速度与生长速度联系起来的模型,解释了代谢环境如何影响酶突变耐受性.
- 描述了在代谢酶内表皮质的结构分布.
- 由TYMS活动所造成的DHFR序列的显著约束.
结论:
- 代谢背景显著调整了酶突变耐受性.
- 揭示了新陈代谢酶中表观症的结构性模式.
- 为设计具有可预测功能相互作用的多酶系统提供了基础.
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