溶液结构的催化域的GCN5基因组酸转移酶结合辅酶A的溶液结构
1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature
|July 14, 1999
概括
甲胺GCN5 (tGCN5) 是一种对基因转录至关重要的基因酸转移酶. 它的催化域结构揭示了辅酶A如何结合以及tGCN5如何与基因素H3相互作用以激活基因表达.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 基因转录包括从基因组蛋白中释放DNA.
- 由基酸转移酶 (HATs) 催化的基酸转化与转录激活有关.
- 甲基GCN5 (tGCN5) 是第一个被确定的转录相关的HAT,酵母GCN5将其招募到促销者中.
研究的目的:
- 确定tGCN5 (残留物47-210) 与辅酶A复合的催化域的溶液结构.
- 为了阐明协酶A和素H3的结合部位.
- 提出一种乙转移反应的机制.
主要方法:
- 核磁共振 (NMR) 光谱法以确定溶液结构.
- 与辅酶A的并发症.
- 用素H3来识别通过化学转移变化的结合部位的定位实验.
主要成果:
- tGCN5催化域的结构揭示了两个不同的域,与其他与GCN5相关的N-乙转移酶不同的是碳氧终端域.
- 发现辅酶A可以结合到位于两个域之间的一个深深的疏水口袋中.
- 素H3结合发生在域边界,与辅酶A结合部位相反.
结论:
- 结构数据为tGCN5.5的催化机制提供了洞察力.
- 建议采用单阶段的乙转移反应机制,涉及与白素126和保存的酸性残留物之间的关键相互作用.
- 这项研究增强了对基因素乙化和基因转录调节的结构基础的理解.
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