使用NADH作为独家辅助因子的真菌细菌甲基基酸盐还原酶的结构和功能特征
Jiacong Li1,2,3, Mingxia Yang4, Weijia Li1,5
1Department of Pathogen Biology, School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
The Biochemical journal
|July 12, 2023
概括
这项研究揭示了Mycobacterium独特的酶5,10-Methylenetetrahydrofolate减少酶 (MTHFR) 如何使用NADH而不是flavin. 这一发现为新的抗菌素药物标提供了洞察力.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 酶学 是一种酶学.
背景情况:
- 5,10-甲基四叶酸减少酶 (MTHFR) 对于叶酸代谢至关重要.
- 来自Mycobacterium smegmatis的MSMEG_6649是一种独特的,不依赖黄素的MTHFR.
- 目前尚不清楚MSMEG_6649的催化机制.
研究的目的:
- 阐明MSMEG_6649.9的素独立催化机制的结构基础.
- 为了确定涉及基质和辅因子结合的关键残留物.
- 探索MSMEG_6649作为一种潜在的抗菌素药物标.
主要方法:
- 进行X射线晶体学以确定MSMEG_6649.9的Apo和NADH结合结构.
- 生物化学测试. 生物化学测试.
- 分子建模和局部定向突变发生.
主要成果:
- 结晶结构显示MSMEG_6649与正规MTHFR相比,有一个更大的FAD相互作用沟.
- MSMEG_6649中的NADH结合部位类似于正规MTHFR中的FAD结合部位.
- 确定和验证了NADH,基质和产品结合的关键残留物.
结论:
- NADH可能作为直接的化物捐赠体起作用,类似于正规MTHFR中的FAD.
- 这些发现为了解MSMEG_6649的催化机制提供了基础.
- MSMEG_6649是开发新抗菌菌疗法的有希望的目标.
关键词:
这种细菌是Mycobacterium smegmatis.10甲基三叶酸减少酶.5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 8 8 8 8 8 8 8 8 8 8 8 8 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 including including including including including including它们是NADH和NADH.在X射线晶体学.这是一种抗菌素药物,是一种抗菌素药物.叶酸是什么 叶酸是什么 叶酸是什么
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