Klyuyeva Alla, Tuganova Alina, Popov Kirill M
Department of Biochemistry and Molecular Genetics, Schools of Medicine and Dentistry, University of Alabama at Birmingham, KAUL 440A, Birmingham, AL 35294, USA.
FEBS Lett. 2007 Jun 26;581(16):2988-92. doi: 10.1016/j.febslet.2007.05.052. Epub 2007 May 29.
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.
二氯乙酸（DCA）是一种有前景的抗癌和抗糖尿病化合物，其作用靶点为线粒体丙酮酸脱氢酶激酶（PDHK）。本研究旨在确定PDHK2的DCA结合位点。在此，我们提供证据表明R114、S83、I157以及在一定程度上的H115对DCA结合至关重要。我们还表明Y80和D117是DCA结合位点与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见解，可能有助于设计新的、更有效的治疗化合物。
