8RTH

Trypanosoma brucei 3-methylcrotonyl-CoA carboxylase

8RTH の概要

• エントリーDOI: 10.2210/pdb8rth/pdb
• EMDBエントリー: 19492
• 分子名称: 3-methylcrotonyl-CoA carboxylase, putative, methylcrotonoyl-CoA carboxylase, 5-(HEXAHYDRO-2-OXO-1H-THIENO[3,4-D]IMIDAZOL-6-YL)PENTANAL (3 entities in total)
• 機能のキーワード: carboxylase, trypanosoma brucei, biosynthetic protein, transferase
• 由来する生物種: Trypanosoma brucei; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 844979.57

構造登録者

Ruiz, F.M.,Plaza-Pegueroles, A.,Fernandez-Tornero, C. (登録日: 2024-01-26, 公開日: 2024-04-17, 最終更新日: 2024-07-24)

主引用文献

Plaza-Pegueroles, A.,Aphasizheva, I.,Aphasizhev, R.,Fernandez-Tornero, C.,Ruiz, F.M.
The cryo-EM structure of trypanosome 3-methylcrotonyl-CoA carboxylase provides mechanistic and dynamic insights into its enzymatic function.
Structure, 32:930-, 2024

PubMed Abstract: 3-Methylcrotonyl-CoA carboxylase (MCC) catalyzes the two-step, biotin-dependent production of 3-methylglutaconyl-CoA, an essential intermediate in leucine catabolism. Given the critical metabolic role of MCC, deficiencies in this enzyme lead to organic aciduria, while its overexpression is linked to tumor development. MCC is a dodecameric enzyme composed of six copies of each α- and β-subunit. We present the cryo-EM structure of the endogenous MCC holoenzyme from Trypanosoma brucei in a non-filamentous state at 2.4 Å resolution. Biotin is covalently bound to the biotin carboxyl carrier protein domain of α-subunits and positioned in a non-canonical pocket near the active site of neighboring β-subunit dimers. Moreover, flexibility of key residues at α-subunit interfaces and loops enables pivoting of α-subunit trimers to partly reduce the distance between α- and β-subunit active sites, required for MCC catalysis. Our results provide a structural framework to understand the enzymatic mechanism of eukaryotic MCCs and to assist drug discovery against trypanosome infections.

PubMed: 38593794
DOI: 10.1016/j.str.2024.03.010

実験手法

ELECTRON MICROSCOPY (2.37 Å)