Biomaterial Database

Amino acid residues responsible for the recognition of dichloroacetate by pyruvate dehydrogenase kinase 2. 2007

Alla Klyuyeva, and Alina Tuganova, and Kirill M Popov

Department of Biochemistry and Molecular Genetics, Schools of Medicine and Dentistry, University of Alabama at Birmingham, KAUL 440A, Birmingham, AL 35294, USA.

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.

UI	MeSH Term	Description	Entries
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D011494	Protein Kinases	A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.	Protein Kinase,Kinase, Protein,Kinases, Protein
D003999	Dichloroacetic Acid	A derivative of ACETIC ACID that contains two CHLORINE atoms attached to its methyl group.	Sodium Dichloroacetate,Bichloroacetic Acid,Potassium Dichloroacetate,Acid, Bichloroacetic,Acid, Dichloroacetic,Dichloroacetate, Potassium,Dichloroacetate, Sodium
D000081382	Pyruvate Dehydrogenase Acetyl-Transferring Kinase	A pyruvate dehydrogenase kinase isozyme located in the mitochondria which converts PYRUVATE to ACETYL CoA in the CITRIC ACID CYCLE, phosphorylates SERINE residues on pyruvate dehydrogenase using ATP, and plays a key role in the regulation of GLUCOSE and fatty acid metabolism.	PDH Kinase,Pyruvate Dehydrogenase (Acetyl-Transferring) Kinase,Pyruvate Dehydrogenase (Lipoamide) Kinase,Pyruvate Dehydrogenase Kinase,Dehydrogenase Kinase, Pyruvate,Kinase, PDH,Kinase, Pyruvate Dehydrogenase,Pyruvate Dehydrogenase Acetyl Transferring Kinase
D000596	Amino Acids	Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.	Amino Acid,Acid, Amino,Acids, Amino
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001665	Binding Sites	The parts of a macromolecule that directly participate in its specific combination with another molecule.	Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D017346	Protein Serine-Threonine Kinases	A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.	Protein-Serine-Threonine Kinases,Serine-Threonine Protein Kinase,Serine-Threonine Protein Kinases,Protein-Serine Kinase,Protein-Serine-Threonine Kinase,Protein-Threonine Kinase,Serine Kinase,Serine-Threonine Kinase,Serine-Threonine Kinases,Threonine Kinase,Kinase, Protein-Serine,Kinase, Protein-Serine-Threonine,Kinase, Protein-Threonine,Kinase, Serine-Threonine,Kinases, Protein Serine-Threonine,Kinases, Protein-Serine-Threonine,Kinases, Serine-Threonine,Protein Kinase, Serine-Threonine,Protein Kinases, Serine-Threonine,Protein Serine Kinase,Protein Serine Threonine Kinase,Protein Serine Threonine Kinases,Protein Threonine Kinase,Serine Threonine Kinase,Serine Threonine Kinases,Serine Threonine Protein Kinase,Serine Threonine Protein Kinases
D047428	Protein Kinase Inhibitors	Agents that inhibit PROTEIN KINASES.	Protein Kinase Inhibitor,Inhibitor, Protein Kinase,Inhibitors, Protein Kinase,Kinase Inhibitor, Protein,Kinase Inhibitors, Protein