ArticleThe EMBO journal2005
Crystal structure of pyruvate dehydrogenase kinase 3 bound to lipoyl domain 2 of human pyruvate dehydrogenase complex.
Article in The EMBO journal, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 113 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
- Targeting cancer metabolism through p-cresol mediated Inhibition of pyruvate dehydrogenase kinase 3 in lung cancer.Scientific reports · 2025Article
- Cholesterol metabolism and intrabacterial potassium homeostasis are intrinsically related in Mycobacterium tuberculosis.PLoS pathogens · 2025Article
- Sensitivity of renal cell carcinoma to cuproptosis: a bioinformatics analysis and experimental verification.Journal of Cancer · 2025Article
- Exploring PDK3 inhibition in lung cancer through drug repurposing for potential therapeutic interventions.Scientific reports · 2024Article
- Investigating Pyruvate Dehydrogenase Kinase 3 Inhibitory Potential of Myricetin Using Integrated Computational and Spectroscopic Approaches.ACS omega · 2024Article
- The Whole Genome DNA Methylation Signatures of Hindlimb Muscles in Chinese Alligators during Hibernation and Active Periods.Animals : an open access journal from MDPI · 2024Article
- Cuproptosis-related genes predict prognosis and trastuzumab therapeutic response in HER2-positive breast cancer.Scientific reports · 2024Article
- Mitochondrial Alpha-Keto Acid Dehydrogenase Complexes: Recent Developments on Structure and Function in Health and Disease.Sub-cellular biochemistry · 2024Review
- Discovery of the 3-Amino-1,2,4-triazine-Based Library as Selective PDK1 Inhibitors with Therapeutic Potential in Highly Aggressive Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2023Article
- Cryo-EM snapshots of a native lysate provide structural insights into a metabolon-embedded transacetylase reaction.Nature communications · 2021Article
- Structure of the native pyruvate dehydrogenase complex reveals the mechanism of substrate insertion.Nature communications · 2021Article
- Article
- Potassium Channels in Cancer.Handbook of experimental pharmacology · 2021Article
- Crystal structure of the catalytic subunit of bovine pyruvate dehydrogenase phosphatase.Acta crystallographica. Section F, Structural biology communications · 2020Article
- Discovery of Hordenine as a Potential Inhibitor of Pyruvate Dehydrogenase Kinase 3: Implication in Lung Cancer Therapy.Biomedicines · 2020Article
- Lipidomic Analysis of Plastidial Octanoyltransferase Mutants ofMetabolites · 2019Article
- Molecular interaction studies on ellagic acid for its anticancer potential targeting pyruvate dehydrogenase kinase 3.RSC advances · 2019Article
- Live-Cell Imaging of Physiologically Relevant Metal Ions Using Genetically Encoded FRET-Based Probes.Cells · 2019Review
- Natural variation ineLife · 2019Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The human pyruvate dehydrogenase complex (PDC) is regulated by reversible phosphorylation by four isoforms of pyruvate dehydrogenase kinase (PDK). PDKs phosphorylate serine residues in the dehydrogenase (E1p) component of PDC, but their amino-acid sequences are unrelated to eukaryotic Ser/Thr/Tyr protein kinases. PDK3 binds to the inner lipoyl domains (L2) from the 60-meric transacetylase (E2p) core of PDC, with concomitant stimulated kinase activity. Here, we present crystal structures of the PDK3-L2 complex with and without bound ADP or ATP. These structures disclose that the C-terminal tail from one subunit of PDK3 dimer constitutes an integral part of the lipoyl-binding pocket in the N-terminal domain of the opposing subunit. The two swapped C-terminal tails promote conformational changes in active-site clefts of both PDK3 subunits, resulting in largely disordered ATP lids in the ADP-bound form. Our structural and biochemical data suggest that L2 binding stimulates PDK3 activity by disrupting the ATP lid, which otherwise traps ADP, to remove product inhibition exerted by this nucleotide. We hypothesize that this allosteric mechanism accounts, in part, for E2p-augmented PDK3 activity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.