ArticleProceedings of the National Academy of Sciences of the United States of America2001
Structure of rat BCKD kinase: nucleotide-induced domain communication in a mitochondrial protein kinase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 84 citations in OpenAlex.
- Branched chain amino acid sufficiency is necessary for proper luteinizing hormone response and testosterone synthesis.Reproductive biology · 2026Article
- Cholesterol metabolism and intrabacterial potassium homeostasis are intrinsically related in Mycobacterium tuberculosis.PLoS pathogens · 2025Article
- Computational structural genomics and clinical evidence suggest BCKDK gain-of-function may cause a potentially asymptomatic maple syrup urine disease phenotype.JIMD reports · 2024Article
- Mitochondrial Alpha-Keto Acid Dehydrogenase Complexes: Recent Developments on Structure and Function in Health and Disease.Sub-cellular biochemistry · 2024Review
- Combining structural and coevolution information to unveil allosteric sites.Chemical science · 2023Article
- BCKDK Promotes Ovarian Cancer Proliferation and Migration by Activating the MEK/ERK Signaling Pathway.Journal of oncology · 2022Article
- Branched-chain Amino Acids: Catabolism in Skeletal Muscle and Implications for Muscle and Whole-body Metabolism.Frontiers in physiology · 2021Review
- Branched chain α-ketoacid dehydrogenase kinase 111-130, a T cell epitope that induces both autoimmune myocarditis and hepatitis in A/J mice.Immunity, inflammation and disease · 2017Article
- Molecular Mechanisms of Enzyme Activation by Monovalent Cations.The Journal of biological chemistry · 2016Review
- Differential inhibition of PDKs by phenylbutyrate and enhancement of pyruvate dehydrogenase complex activity by combination with dichloroacetate.Journal of inherited metabolic disease · 2015Article
- The role of monovalent cations in the ATPase reaction of DNA gyrase.Acta crystallographica. Section D, Biological crystallography · 2015Article
- Benzothiophene carboxylate derivatives as novel allosteric inhibitors of branched-chain α-ketoacid dehydrogenase kinase.The Journal of biological chemistry · 2014Article
- Structure-based design and mechanisms of allosteric inhibitors for mitochondrial branched-chain α-ketoacid dehydrogenase kinase.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Phenylbutyrate therapy for pyruvate dehydrogenase complex deficiency and lactic acidosis.Science translational medicine · 2013Article
- Pyruvate Dehydrogenase Kinases in the Nervous System: Their Principal Functions in Neuronal-glial Metabolic Interaction and Neuro-metabolic Disorders.Current neuropharmacology · 2012Article
- Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy.Science (New York, N.Y.) · 2012Article
- Comparative homology modeling of pyruvate dehydrogenase kinase isozymes from Xenopus tropicalis reveals structural basis for their subfunctionalization.Journal of molecular modeling · 2012Article
- Potassium ions are required for nucleotide-induced closure of gyrase N-gate.The Journal of biological chemistry · 2012Article
- Intrinsic negative feedback governs activation surge in two-component regulatory systems.Molecular cell · 2012Article
- Structural and enzymatic insights into the ATP binding and autophosphorylation mechanism of a sensor histidine kinase.The Journal of biological chemistry · 2010Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Mitochondrial protein kinases (mPKs) are molecular switches that down-regulate the oxidation of branched-chain alpha-ketoacids and pyruvate. Elevated levels of these metabolites are implicated in disease states such as insulin-resistant Type II diabetes, branched-chain ketoaciduria, and primary lactic acidosis. We report a three-dimensional structure of a member of the mPK family, rat branched-chain alpha-ketoacid dehydrogenase kinase (BCK). BCK features a characteristic nucleotide-binding domain and a four-helix bundle domain. These two domains are reminiscent of modules found in protein histidine kinases (PHKs), which are involved in two-component signal transduction systems. Unlike PHKs, BCK dimerizes through direct interaction of two opposing nucleotide-binding domains. Nucleotide binding to BCK is uniquely mediated by both potassium and magnesium. Binding of ATP induces disorder-order transitions in a loop region at the nucleotide-binding site. These structural changes lead to the formation of a quadruple aromatic stack in the interface between the nucleotide-binding domain and the four-helix bundle domain, where they induce a movement of the top portion of two helices. Phosphotransfer induces further ordering of the loop region, effectively trapping the reaction product ADP, which explains product inhibition in mPKs. The BCK structure is a prototype for all mPKs and will provide a framework for structure-assisted inhibitor design for this family of kinases.
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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.