8RTH
Trypanosoma brucei 3-methylcrotonyl-CoA carboxylase
Summary for 8RTH
| Entry DOI | 10.2210/pdb8rth/pdb |
| EMDB information | 19492 |
| Descriptor | 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) |
| Functional Keywords | carboxylase, trypanosoma brucei, biosynthetic protein, transferase |
| Biological source | Trypanosoma brucei More |
| Total number of polymer chains | 12 |
| Total formula weight | 844979.57 |
| Authors | Ruiz, F.M.,Plaza-Pegueroles, A.,Fernandez-Tornero, C. (deposition date: 2024-01-26, release date: 2024-04-17, Last modification date: 2024-07-24) |
| Primary citation | 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 Cited by 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: 38593794DOI: 10.1016/j.str.2024.03.010 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.37 Å) |
Structure validation
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