Theoretical study revealing the functioning of a novel combination of catalytic motifs in histone deacetylase
Theoretical study revealing the functioning of a novel combination of catalytic motifs in histone deacetylase
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DOI：
10.1016/j.bmc.2005.04.001
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发表时间：
2005-06-02
影响因子：
3.5
通讯作者：
Geerlings, P
中科院分区：
文献类型：
--
作者：
Vanommeslaeghe, K;De Proft, F;Geerlings, P
组蛋白去乙酰化酶（HDAC）作为治疗细胞增殖性疾病如癌症的靶标最近引起了相当大的兴趣。在目前的工作中，HDAC的活性中心的化学性质进行了理论研究，在高计算水平。证据收集了一种新的催化机制，这不同于以前的建议，在本机质子化状态的组氨酸-天冬氨酸二联体，并在去质子化的水作为一个独特的步骤中的机制。(c)2005爱思唯尔有限公司保留所有权利。
Histone deacetylases (HDACs) have recently attracted considerable interest as targets in the treatment of cell proliferative diseases such as cancer. In the present work, the chemical properties of the active site of HDAC were theoretically investigated at a high computational level. Evidence was gathered for a novel catalytic mechanism, which differs from a previous proposal in the native protonation state of the His-Asp dyads, and in the deprotonation of water as a distinct step in the mechanism. (c) 2005 Elsevier Ltd. All rights reserved.