在辅因子生物合成中,由GTP 3',8-环酶启动C-终端甘氨酸入的基因
Bradley M Hover1, Kenichi Yokoyama
1Department of Biochemistry, Duke University Medical Center , Durham, North Carolina 27710, United States.
Journal of the American Chemical Society
|February 21, 2015
概括
在MOCS1A酶中的GG动机对于辅因子生物合成至关重要. 这种基因的突变破坏了酶的功能,导致致命的代谢障碍Moco缺乏症 (MoCD).
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 酶学 是一种酶学.
背景情况:
- 辅因子 (Moco) 对所有生命中的氧化还原反应至关重要.
- 摩可缺乏症 (Moco deficiency, MoCD) 是一种致命的遗传代谢障碍,由摩可生物合成缺陷引起.
- MOCS1A突变导致超过50%的人类MoCD病例,影响GTP转化.
研究的目的:
- 研究MOCS1A.中保存的C端GG基因的功能作用.
- 阐明GG基因突变导致Moco缺陷的机制.
主要方法:
- 利用MOAA,MOCS1A的细菌同类物,作为一个模型系统.
- 执行了GG动机突变的功能性特征.
- 使用合成来挽救酶活性.
- 进行生物化学测试以分析酶-基质和酶-辅助因子相互作用.
主要成果:
- GG图案对于MoaA的GTP 3',8环酶活性至关重要.
- 合成的C端恢复了GG基因突变的活性.
- 包括GG图案在内的C端尾与SAM结合口袋相互作用.
- 这种相互作用对S-adenosyl-l-methionine (SAM) 结合和激素启动至关重要.
结论:
- 带有GG图案的C端尾部对于启动MoaA.A.中的激进反应至关重要.
- 这种动机的损伤导致催化功能的完全丧失.
- 这种功能障碍解释了MOCS1A突变患者MoCD的分子基础.
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