EMD-33729

Single-particle
2.2 Å
EMD-33729 Deposition: 29/06/2022
Map released: 05/07/2023
Last modified: 27/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-33729

Human propionyl-coenzyme A carboxylase

EMD-33729

Single-particle
2.2 Å
EMD-33729 Deposition: 29/06/2022
Map released: 05/07/2023
Last modified: 27/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens
Sample: Human propionyl-coenzyme A carboxylase heterododecomer
Fitted models: 7ybu (Avg. Q-score: 0.54)

Deposition Authors: Su JY , Liu DS
Structural insight into synergistic activation of human 3-methylcrotonyl-CoA carboxylase.
Su J , Tian X, Cheng H , Liu D, Wang Z, Sun S , Wang HW , Sui SF
(2024) Nat Struct Mol Biol
PUBMED: 39223421
DOI: doi:10.1038/s41594-024-01379-3
ISSN: 1545-9985
Abstract:
The enzymes 3-methylcrotonyl-coenzyme A (CoA) carboxylase (MCC), pyruvate carboxylase and propionyl-CoA carboxylase belong to the biotin-dependent carboxylase family located in mitochondria. They participate in various metabolic pathways in human such as amino acid metabolism and tricarboxylic acid cycle. Many human diseases are caused by mutations in those enzymes but their structures have not been fully resolved so far. Here we report an optimized purification strategy to obtain high-resolution structures of intact human endogenous MCC, propionyl-CoA carboxylase and pyruvate carboxylase in different conformational states. We also determine the structures of MCC bound to different substrates. Analysis of MCC structures in different states reveals the mechanism of the substrate-induced, multi-element synergistic activation of MCC. These results provide important insights into the catalytic mechanism of the biotin-dependent carboxylase family and are of great value for the development of new drugs for the treatment of related diseases.