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Amino acid residues responsible for the recognition of dichloroacetate by pyruvate dehydrogenase kinase 2
Author(s) -
Klyuyeva Alla,
Tuganova Alina,
Popov Kirill M.
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.05.052
Subject(s) - pyruvate dehydrogenase kinase , pyruvate dehydrogenase complex , biochemistry , chemistry , dihydrolipoyl transacetylase , binding site , pyruvate kinase , mechanism of action , oxoglutarate dehydrogenase complex , pyruvate dehydrogenase phosphatase , kinase , enzyme , glycolysis , in vitro
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.