8GJU
Crystal structure of human methylmalonyl-CoA mutase (MMUT) in complex with methylmalonic acidemia type A protein (MMAA), coenzyme A, and GDP
Summary for 8GJU
| Entry DOI | 10.2210/pdb8gju/pdb |
| Descriptor | Methylmalonic aciduria type A protein, mitochondrial, Methylmalonyl-CoA mutase, mitochondrial, GUANOSINE-5'-DIPHOSPHATE, ... (6 entities in total) |
| Functional Keywords | protein-protein complex, isomerase, gtpase, g-protein, cobalamin, vitamin b12, transport, organometallic cofactor, isomerase-hydrolase complex, isomerase/hydrolase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 8 |
| Total formula weight | 491855.50 |
| Authors | Mascarenhas, R.M.,Ruetz, M.,Gouda, H.,Yaw, M.,Banerjee, R. (deposition date: 2023-03-16, release date: 2023-08-09, Last modification date: 2024-05-22) |
| Primary citation | Mascarenhas, R.,Ruetz, M.,Gouda, H.,Heitman, N.,Yaw, M.,Banerjee, R. Architecture of the human G-protein-methylmalonyl-CoA mutase nanoassembly for B 12 delivery and repair. Nat Commun, 14:4332-4332, 2023 Cited by PubMed Abstract: G-proteins function as molecular switches to power cofactor translocation and confer fidelity in metal trafficking. The G-protein, MMAA, together with MMAB, an adenosyltransferase, orchestrate cofactor delivery and repair of B-dependent human methylmalonyl-CoA mutase (MMUT). The mechanism by which the complex assembles and moves a >1300 Da cargo, or fails in disease, are poorly understood. Herein, we report the crystal structure of the human MMUT-MMAA nano-assembly, which reveals a dramatic 180° rotation of the B domain, exposing it to solvent. The complex, stabilized by MMAA wedging between two MMUT domains, leads to ordering of the switch I and III loops, revealing the molecular basis of mutase-dependent GTPase activation. The structure explains the biochemical penalties incurred by methylmalonic aciduria-causing mutations that reside at the MMAA-MMUT interfaces we identify here. PubMed: 37468522DOI: 10.1038/s41467-023-40077-4 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.79 Å) |
Structure validation
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