8V3V
ACAD11 D753N with 4-phosphovaleryl-CoA
Summary for 8V3V
| Entry DOI | 10.2210/pdb8v3v/pdb |
| Related | 8V3U |
| EMDB information | 42955 |
| Descriptor | Acyl-Coenzyme A dehydrogenase family, member 11, FLAVIN-ADENINE DINUCLEOTIDE (2 entities in total) |
| Functional Keywords | acyl-coa dehydrogenases, dihedral, mitochondrial, oxidoreductase |
| Biological source | Mus musculus (house mouse) |
| Total number of polymer chains | 4 |
| Total formula weight | 352471.04 |
| Authors | Zhang, J.,Bartlett, A.,Rashan, E.,Yuan, P.,Pagliarini, D. (deposition date: 2023-11-28, release date: 2024-12-11, Last modification date: 2025-10-01) |
| Primary citation | Rashan, E.H.,Bartlett, A.K.,Khana, D.B.,Zhang, J.,Jain, R.,Wade, G.,Abriata, L.A.,Smith, A.J.,Baker, Z.N.,Cook, T.,Caldwell, A.,Chevalier, A.R.,Forny, P.,Pfleger, B.F.,Peraro, M.D.,Yuan, P.,Amador-Noguez, D.,Simcox, J.A.,Pagliarini, D.J. ACAD10 and ACAD11 enable mammalian 4-hydroxy acid lipid catabolism. Nat.Struct.Mol.Biol., 32:1622-1632, 2025 Cited by PubMed Abstract: Fatty acid β-oxidation is a central catabolic pathway with broad health implications. However, various fatty acids, including 4-hydroxy acids (4-HAs), are largely incompatible with β-oxidation machinery before being modified. Here we reveal that two atypical acyl-CoA dehydrogenases, ACAD10 and ACAD11, drive 4-HA catabolism in mice. Unlike other ACADs, ACAD10 and ACAD11 feature kinase domains that phosphorylate the 4-hydroxy position as a requisite step in converting 4-hydroxyacyl-CoAs into conventional 2-enoyl-CoAs. Through cryo-electron microscopy and molecular modeling, we identified an atypical dehydrogenase binding pocket capable of accommodating this phosphorylated intermediate. We further show that ACAD10 is mitochondrial and necessary for catabolizing shorter-chain 4-HAs, whereas ACAD11 is peroxisomal and enables longer-chain 4-HA catabolism. Mice lacking ACAD11 accumulate 4-HAs in their plasma and females are susceptible to body weight and fat gain, concurrent with decreased adipocyte differentiation and adipokine expression. Collectively, we present that ACAD10 and ACAD11 are the primary gatekeepers of mammalian 4-HA catabolism. PubMed: 40537578DOI: 10.1038/s41594-025-01596-4 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.6 Å) |
Structure validation
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