ArticleThe Journal of biological chemistry2008
Structural and functional insights into the molecular mechanisms responsible for the regulation of pyruvate dehydrogenase kinase 2.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- The Pyruvate Dehydrogenase Complex: A 90-Year-Old Enigma Shaping the Future of Structural Enzymology.Advances in experimental medicine and biology · 2026Review
- Mitochondrial Alpha-Keto Acid Dehydrogenase Complexes: Recent Developments on Structure and Function in Health and Disease.Sub-cellular biochemistry · 2024Review
- A novel organic arsenic derivative MZ2 remodels metabolism and triggers mtROS-mediated apoptosis in acute myeloid leukemia.Journal of cancer research and clinical oncology · 2023Article
- Dynamic regulation of mitochondrial pyruvate metabolism is necessary for orthotopic pancreatic tumor growth.Cancer & metabolism · 2021Article
- Structure of the native pyruvate dehydrogenase complex reveals the mechanism of substrate insertion.Nature communications · 2021Article
- Detailed evaluation of pyruvate dehydrogenase complex inhibition in simulated exercise conditions.Biophysical journal · 2021Article
- Article
- Global view of cognate kinase activation by the human pyruvate dehydrogenase complex.Scientific reports · 2017Article
- Global Kinetic Analysis of Mammalian E3 Reveals pH-dependent NAD+/NADH Regulation, Physiological Kinetic Reversibility, and Catalytic Optimum.The Journal of biological chemistry · 2016Article
- Article
- A pH-dependent kinetic model of dihydrolipoamide dehydrogenase from multiple organisms.Biophysical journal · 2014Article
- Regulation of pyruvate metabolism and human disease.Cellular and molecular life sciences : CMLS · 2014Review
- The pyruvate dehydrogenase complexes: structure-based function and regulation.The Journal of biological chemistry · 2014Review
- Structure-guided development of specific pyruvate dehydrogenase kinase inhibitors targeting the ATP-binding pocket.The Journal of biological chemistry · 2014Article
- Inactivation of pyruvate dehydrogenase kinase 2 by mitochondrial reactive oxygen species.The Journal of biological chemistry · 2012Article
- Comparative homology modeling of pyruvate dehydrogenase kinase isozymes from Xenopus tropicalis reveals structural basis for their subfunctionalization.Journal of molecular modeling · 2012Article
- Pivotal role of the C-terminal DW-motif in mediating inhibition of pyruvate dehydrogenase kinase 2 by dichloroacetate.The Journal of biological chemistry · 2009Article
- Pyruvate dehydrogenase kinase-4 structures reveal a metastable open conformation fostering robust core-free basal activity.The Journal of biological chemistry · 2008Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
PDHK2 is a mitochondrial protein kinase that phosphorylates pyruvate dehydrogenase complex, thereby down-regulating the oxidation of pyruvate. Here, we present the crystal structure of PDHK2 bound to the inner lipoyl-bearing domain of dihydrolipoamide transacetylase (L2) determined with or without bound adenylyl imidodiphosphate. Both structures reveal a PDHK2 dimer complexed with two L2 domains. Comparison with apo-PDHK2 shows that L2 binding causes rearrangements in PDHK2 structure that affect the L2- and E1-binding sites. Significant differences are found between PDHK2 and PDHK3 with respect to the structure of their lipoyllysine-binding cavities, providing the first structural support to a number of studies showing that these isozymes are markedly different with respect to their affinity for the L2 domain. Both structures display a novel type II potassium-binding site located on the PDHK2 interface with the L2 domain. Binding of potassium ion at this site rigidifies the interface and appears to be critical in determining the strength of L2 binding. Evidence is also presented that potassium ions are indispensable for the cross-talk between the nucleotide- and L2-binding sites of PDHK2. The latter is believed to be essential for the movement of PDHK2 along the surface of the transacetylase scaffold.
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