通过乙化对PKM的异形特异性调节
Dariia Pavlenko1, Joaquin Tamargo-Azpilicueta2, Hila Nudelman1
1Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
概括
乙化调节了酸盐激酶 (PK) 的活性. 氨酸115的局部特异性乙化抑制了PKM1和PKM2,而氨酸305的乙化只影响PKM2,显示出异构体特异性调节.
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:
- 酸盐激酶 (PK) 是一个关键的糖解酶,调节细胞代谢.
- 翻译后的Nε-lysine乙化是PK活动的关键调节机制.
- 对对PKM1和PKM2异型的乙化作用的理解有限.
研究的目的:
- 综合调查特定位点乙化对PKM1和PKM2.0的结构,功能和监管影响.
- 阐明由乙化介导的异形特异性调节机制.
主要方法:
- 在基因编码中将乙化素纳入PKM变体.
- 在细菌和培养的哺乳动物细胞中表达.
- 综合生化,结构和计算分析.
主要成果:
- lysine 115 (K115) 的乙化通过稳定一个封闭的活性位子构造来抑制PKM1和PKM2.
- 氨酸305 (K305) 的乙化抑制了PKM2,但不能抑制PKM1的活性或寡合化.
- 确定了保留和异形特异性乙化介导调节通路.
结论:
- 乙化K115代表了PK异型的保护性调节机制.
- 乙化K305证明了PKM2.2的异形特异性调节.
- 这些发现突出了对酸盐激酶的多种乙化驱动的调节策略.
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