由Haemophilus ducreyiyi的NadV催化NMN合成的结构基础
Zheng-Juan Wang1, Jia Yuan1, Lin Tang1
1Department of Neurology, State Key Lab of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, Sichuan, China; Institute of Brain Science and Brain-inspired Technology of West China Hospital, Sichuan University, Chengdu, China.
Biochemical and biophysical research communications
|November 7, 2024
概括
尼古丁胺胺氨基二核酸 (NAD+) 对细胞功能至关重要. 这项研究使大肠杆菌产生NMN,NAD+前体,并确定了Nadv的结构,揭示了NMN合成的洞察力.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 尼古丁胺胺氨基二核酸 (NAD+) 对细胞过程至关重要,对与年龄相关的疾病具有治疗潜力.
- 尼古丁胺胺单核酸 (NMN) 是NAD+的直接前体,其补充可以改善各种健康状况.
- 大肠杆菌被设计用于尼古丁胺酸基转移酶 (Nampt) 的异质表达,以合成NAD+衍生物.
研究的目的:
- 通过Nadv.阐明NMN合成的分子机制.
- 确定Nadv与NAM和NMN复合的3D结构.
- 为工程Nadv提供一个基础,以实现高效的生物NMN生产.
主要方法:
- 埃舍里希亚大肠杆菌的工程用于尼古丁胺酸基转移酶 (Nampt) 的异质表达.
- 确定与尼古丁胺 (NAM) 和NMN复合的Nadv的3D晶体结构.
- 在Nadv.内对NAM和NMN结合部位的结构分析.
主要成果:
- 在催化和全位点上,NAM与Nadv结合,而NMN仅在催化位点结合.
- 由于电子密度分散,Nadv结构中发现缺少一个灵活的循环 (β15-β16).
- 与其他Nampt结构相比,Nadv在催化部位附近发现了额外的12氨基酸循环.
结论:
- 确定的结构为Nadv介导的NMN合成的催化机制提供了关键的见解.
- 了解Nadv的结构特征,有助于其对增强生物NMN生产的潜在工程.
- 这项研究支持NMN作为治疗剂和抗衰老化合物的发展,通过改进生物技术合成.
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