Amino acid residues responsible for the recognition of dichloroacetate by pyruvate dehydrogenase kinase 2.
Amino acid residues responsible for the recognition of dichloroacetate by pyruvate dehydrogenase kinase 2.
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负责丙酮酸脱氢酶激酶 2 识别二氯乙酸的氨基酸残基。
DOI：
10.1016/j.febslet.2007.05.052
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发表时间：
2007
期刊：
影响因子：
3.5
通讯作者：
Popov,KirillM
中科院分区：
文献类型：
--
作者：
Klyuyeva,Alla;Tuganova,Alina;Popov,KirillM
二氯乙酸 (DCA) 是一种有前途的抗癌和抗糖尿病化合物，靶向线粒体丙酮酸脱氢酶激酶 (PDHK)。进行这项研究是为了绘制 PDHK2 的 DCA 结合位点图谱。在这里，我们提供的证据表明 R114、S83、I157 以及在某种程度上 H115 对于 DCA 结合至关重要。我们还表明，Y80 和 D117 是 DCA 结合位点和 PDHK2 活性位点之间通讯所必需的。这些观察结果为 DCA 作用机制提供了重要的见解，可能有助于设计新的、更有效的治疗化合物。
Dichloroacetate (DCA) is a promising anticancer and antidiabetic compound targeting the mitochondrial pyruvate dehydrogenase kinase (PDHK). This study was undertaken in order to map the DCA-binding site of PDHK2. Here, we present evidence that R114, S83, I157 and, to some extent, H115 are essential for DCA binding. We also show that Y80 and D117 are required for the communication between the DCA-binding site and active site of PDHK2. These observations provide important insights into the mechanism of DCA action that may be useful for the design of new, more potent therapeutic compounds.