8J4Z

Human 3-methylcrotonyl-CoA carboxylase in BCCP-CTS state with substrate

8J4Z の概要

• エントリーDOI: 10.2210/pdb8j4z/pdb
• EMDBエントリー: 35980
• 分子名称: 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)
• 機能のキーワード: mcc, mitochondria, 3-methylcrotonyl-coa, cytosolic protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 858407.93

構造登録者

Liu, D.S.,Su, J.Y. (登録日: 2023-04-21, 公開日: 2024-04-24, 最終更新日: 2025-02-05)

主引用文献

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., 32:73-85, 2025

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: 39223421
DOI: 10.1038/s41594-024-01379-3

実験手法

ELECTRON MICROSCOPY (2.73 Å)