Molecular architecture of the acetohydroxyacid synthase holoenzyme
Molecular architecture of the acetohydroxyacid synthase holoenzyme
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乙酰羟酸合酶全酶的分子结构
DOI：
10.1042/bcj20200292
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发表时间：
2020
影响因子：
4.1
通讯作者：
Shen Yuequan
中科院分区：
文献类型：
--
作者：
Zhang Yingying;Li Yang;Liu Xiao;Sun Jixue;Li Xin;Lin Jianping;Yang Xue;Xi Zhen;Shen Yuequan
乙酰羟酸合酶（AHAS）全酶催化支链氨基酸生物合成的第一步，对植物和细菌至关重要。它由调节亚基（RSU）和催化亚基（CSU）组成。几十年来，AHAS 全酶的变构机制仍然难以捉摸。在这里，我们确定了 AHAS 全酶的晶体结构，揭示了 RSU 和 CSU 在 A2B2 模式下的关联。结构分析结合突变研究表明，RSU二聚体与CSU二聚体形成广泛的相互作用，其中R32和D120之间的保守盐桥可能作为打开CSU激活环的触发器，导致RSU激活CSU。我们的研究揭示了 AHAS 全酶的激活机制。
The acetohydroxyacid synthase (AHAS) holoenzyme catalyzes the first step of branch-chain amino acid biosynthesis and is essential for plants and bacteria. It consists of a regulatory subunit (RSU) and a catalytic subunit (CSU). The allosteric mechanism of the AHAS holoenzyme has remained elusive for decades. Here, we determined the crystal structure of the AHAS holoenzyme, revealing the association between the RSU and CSU in an A2B2 mode. Structural analysis in combination with mutational studies demonstrated that the RSU dimer forms extensive interactions with the CSU dimer, in which a conserved salt bridge between R32 and D120 may act as a trigger to open the activation loop of the CSU, resulting in the activation of the CSU by the RSU. Our study reveals the activation mechanism of the AHAS holoenzyme.