8JXN
Human 3-methylcrotonyl-CoA carboxylase in BCCP-H1 state with MCoA
Summary for 8JXN
| Entry DOI | 10.2210/pdb8jxn/pdb |
| EMDB information | 36706 |
| Descriptor | Methylcrotonoyl-CoA carboxylase beta chain, mitochondrial, Methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial, 5-(HEXAHYDRO-2-OXO-1H-THIENO[3,4-D]IMIDAZOL-6-YL)PENTANAL, ... (4 entities in total) |
| Functional Keywords | mcc, mitochondrial, cytosolic protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 12 |
| Total formula weight | 858407.93 |
| Authors | Liu, D.S.,Su, J.Y.,Tian, X.Y. (deposition date: 2023-06-30, release date: 2024-07-03, Last modification date: 2024-11-27) |
| Primary citation | Su, J.,Tian, X.,Cheng, H.,Liu, D.,Wang, Z.,Sun, S.,Wang, H.W.,Sui, S.F. Structural insight into synergistic activation of human 3-methylcrotonyl-CoA carboxylase. Nat.Struct.Mol.Biol., 2024 Cited by PubMed 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. PubMed: 39223421DOI: 10.1038/s41594-024-01379-3 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
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