ArticleNature2010
Crystal structure of the alpha(6)beta(6) holoenzyme of propionyl-coenzyme A carboxylase.
Article in Nature, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 98 citations in OpenAlex.
- Article
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- Structural basis for substrate specificity and MSMEG_0435-0436 binding by the mycobacterial long-chain acyl-CoA carboxylase complex.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- RNA-Based Therapies for Inherited Metabolic Disorders.Journal of inherited metabolic disease · 2026Review
- Structural insight into synergistic activation of human 3-methylcrotonyl-CoA carboxylase.Nature structural & molecular biology · 2025Article
- Article
- Sample optimizations to enable the structure determination of biotin-dependent carboxylases.Methods in enzymology · 2024Article
- Systemic gene therapy using an AAV44.9 vector rescues a neonatal lethal mouse model of propionic acidemia.Molecular therapy. Methods & clinical development · 2023Article
- Discovery, structure, and function of filamentous 3-methylcrotonyl-CoA carboxylase.Structure (London, England : 1993) · 2023Article
- Sex-Gender-Based Differences in Metabolic Diseases.Handbook of experimental pharmacology · 2023Review
- CryoEM reveals oligomeric isomers of a multienzyme complex and assembly mechanics.Journal of structural biology: X · 2023Article
- The opportunistic pathogen Pseudomonas aeruginosa exploits bacterial biotin synthesis pathway to benefit its infectivity.PLoS pathogens · 2023Article
- CryoEM structural exploration of catalytically active enzyme pyruvate carboxylase.Nature communications · 2022Article
- Genetic Characterization of the Ibuprofen-Degradative Pathway of Rhizorhabdus wittichii MPO218.Applied and environmental microbiology · 2022Article
- Functional Analysis of theInternational journal of molecular sciences · 2021Article
- Biochemical and structural characterization of the BioZ enzyme engaged in bacterial biotin synthesis pathway.Nature communications · 2021Article
- Biocatalytic C-C Bond Formation for One Carbon Resource Utilization.International journal of molecular sciences · 2021Review
- MCCC2 promotes HCC development by supporting leucine oncogenic function.Cancer cell international · 2021Article
- Dual mRNA therapy restores metabolic function in long-term studies in mice with propionic acidemia.Nature communications · 2020Article
- A novel delins (c.773_819+47delinsAA) mutation of the PCCA gene associated with neonatal-onset propionic acidemia: a case report.BMC medical genetics · 2020Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Propionyl-coenzyme A carboxylase (PCC), a mitochondrial biotin-dependent enzyme, is essential for the catabolism of the amino acids Thr, Val, Ile and Met, cholesterol and fatty acids with an odd number of carbon atoms. Deficiencies in PCC activity in humans are linked to the disease propionic acidaemia, an autosomal recessive disorder that can be fatal in infants. The holoenzyme of PCC is an alpha(6)beta(6) dodecamer, with a molecular mass of 750 kDa. The alpha-subunit contains the biotin carboxylase (BC) and biotin carboxyl carrier protein (BCCP) domains, whereas the beta-subunit supplies the carboxyltransferase (CT) activity. Here we report the crystal structure at 3.2-A resolution of a bacterial PCC alpha(6)beta(6) holoenzyme as well as cryo-electron microscopy (cryo-EM) reconstruction at 15-A resolution demonstrating a similar structure for human PCC. The structure defines the overall architecture of PCC and reveals unexpectedly that the alpha-subunits are arranged as monomers in the holoenzyme, decorating a central beta(6) hexamer. A hitherto unrecognized domain in the alpha-subunit, formed by residues between the BC and BCCP domains, is crucial for interactions with the beta-subunit. We have named it the BT domain. The structure reveals for the first time the relative positions of the BC and CT active sites in the holoenzyme. They are separated by approximately 55 A, indicating that the entire BCCP domain must translocate during catalysis. The BCCP domain is located in the active site of the beta-subunit in the current structure, providing insight for its involvement in the CT reaction. The structural information establishes a molecular basis for understanding the large collection of disease-causing mutations in PCC and is relevant for the holoenzymes of other biotin-dependent carboxylases, including 3-methylcrotonyl-CoA carboxylase (MCC) and eukaryotic acetyl-CoA carboxylase (ACC).
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