Structural highlights
FunctionPublication Abstract from PubMed3-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 alpha- and beta-subunit. We present the cryo-EM structure of the endogenous MCC holoenzyme from Trypanosoma brucei in a non-filamentous state at 2.4 A resolution. Biotin is covalently bound to the biotin carboxyl carrier protein domain of alpha-subunits and positioned in a non-canonical pocket near the active site of neighboring beta-subunit dimers. Moreover, flexibility of key residues at alpha-subunit interfaces and loops enables pivoting of alpha-subunit trimers to partly reduce the distance between alpha- and beta-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. The cryo-EM structure of trypanosome 3-methylcrotonyl-CoA carboxylase provides mechanistic and dynamic insights into its enzymatic function.,Plaza-Pegueroles A, Aphasizheva I, Aphasizhev R, Fernandez-Tornero C, Ruiz FM Structure. 2024 Jul 11;32(7):930-940.e3. doi: 10.1016/j.str.2024.03.010. Epub , 2024 Apr 8. PMID:38593794[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
This page was last modified 06:55, 24 July 2024.