Crystal Structure of the Human Histone Methyltransferase ASH1L Catalytic Domain and Its Implications for the Regulatory Mechanism
Crystal Structure of the Human Histone Methyltransferase ASH1L Catalytic Domain and Its Implications for the Regulatory Mechanism
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DOI：
10.1074/jbc.m110.203380
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发表时间：
2011-03-11
影响因子：
4.8
通讯作者：
Song, Ji-Joon
中科院分区：
文献类型：
--
作者：
An, Sojin;Yeo, Kwon Joo;Song, Ji-Joon
缺失、小或同源异型盘1（Ash 1）是一种参与基因激活的三胸组组蛋白甲基转移酶。虽然有许多已知的组蛋白甲基转移酶，其调控机制知之甚少。在这里，我们提出了人类ASH 1 L催化结构域的晶体结构，显示其底物结合口袋从后SET域的环阻断。在这种配置中，环限制了基板对活性位点的访问。环的突变刺激ASH 1 L组蛋白甲基转移酶活性，表明ASH 1 L活性可能通过环从后SET域调节。此外，我们发现，人类ASH 1 L特异性甲基化组蛋白H3 Lys-36。我们的数据暗示，可能有一个调控机制的ASH 1 L组蛋白甲基转移酶。
Absent, small, or homeotic disc1 (Ash1) is a trithorax group histone methyltransferase that is involved in gene activation. Although there are many known histone methyltransferases, their regulatory mechanisms are poorly understood. Here, we present the crystal structure of the human ASH1L catalytic domain, showing its substrate binding pocket blocked by a loop from the post-SET domain. In this configuration, the loop limits substrate access to the active site. Mutagenesis of the loop stimulates ASH1L histone methyltransferase activity, suggesting that ASH1L activity may be regulated through the loop from the post-SET domain. In addition, we show that human ASH1L specifically methylates histone H3 Lys-36. Our data implicate that there may be a regulatory mechanism of ASH1L histone methyltransferases.