-硫协调化学驱动 B12 负载到甲合成酶
Romila Mascarenhas1, Arkajit Guha1, Zhu Li1
1Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, United States.
Journal of the American Chemical Society
|November 2, 2023
概括
人类可巴胺贩运蛋白MMADHC使用不稳定的-硫键将维生素B12转移到合成酶. 这种机制解释了MMADHC变体患者的同胞性尿症.
科学领域:
- 生物化学
- 分子生物学
- 生物物理
背景情况:
- 科巴胺 (维生素B12) 是哺乳动物中必不可少的有机金属辅因子.
- 科巴胺通过伴奏物被运送到其向酶 - - 氨酸合成酶.
- 在生物系统中,-硫 (Co-S) 协调化学通常是不稳定的和罕见的.
研究的目的:
- 调查人类可巴胺贩运蛋白MMADHC将可巴胺释放到氨酸合成酶的机制.
- 阐明 Co-S 协调性在胺转移中的作用.
主要方法:
- 生物化学测定用于研究蛋白质与蛋白质相互作用和辅因子转移.
- 对MMADHC-可巴胺和MMADHC-氨酸合成复合物的结构分析 (隐含).
- 对MMADHC的临床变体进行分析,以评估生理相关性.
主要成果:
- MMADHC使用Cys-261作为可巴胺的下轴联体.
- 与甲氨酸合成酶的复合形成触发了联体的损失,形成了五坐标的甲胺.
- Cys-262促进核友转移,完成辅因子转移并释放氧化的MMADHC.
结论:
- MMADHC利用Co-S键的化学可变性进行高效的胺转移.
- 这种已识别的机制为MMADHC变体相关的同胞性尿症提供了分子解释.
- 这项研究揭示了不稳定的Co-S协调在辅助因子贩运中的新生物学作用.
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