{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["8"],"submitter":["Ju K"],"pubmed_abstract":["Isovaleryl-CoA (coenzyme A) dehydrogenase (IVD) plays a pivotal role in the catabolism of leucine, converting isovaleryl-CoA to 3-methylcrotonyl-CoA. Dysfunction of IVD is linked to isovaleric acidemia (IVA), a rare metabolic disorder characterized by the accumulation of toxic metabolites. In this study, we present the cryo-electron microscopy structures of human IVD, resolved both in its apo form and in complex with its substrates, isovaleryl-CoA and butyryl-CoA. Our findings reveal a tetrameric architecture with distinct substrate-binding pockets that facilitate the enzyme's preference for short branched-chain acyl-CoAs. Key residues involved in FAD binding and substrate interaction were identified, elucidating the catalytic mechanism of IVD. Additionally, we investigated the impact of v"],"journal":["Research (Washington, D.C.)"],"pagination":["0661"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12369846"],"repository":["biostudies-literature"],"pubmed_title":["Structural Insights into Isovaleryl-Coenzyme A Dehydrogenase: Mechanisms of Substrate Specificity and Implications of Isovaleric Acidemia-Associated Mutations."],"pmcid":["PMC12369846"],"pubmed_authors":["Luan X","Ju K","Li Q","Chen H","Jin Y","Zhang S","Su G","Bai F","Xu Y"],"additional_accession":[]},"is_claimable":false,"name":"Structural Insights into Isovaleryl-Coenzyme A Dehydrogenase: Mechanisms of Substrate Specificity and Implications of Isovaleric Acidemia-Associated Mutations.","description":"Isovaleryl-CoA (coenzyme A) dehydrogenase (IVD) plays a pivotal role in the catabolism of leucine, converting isovaleryl-CoA to 3-methylcrotonyl-CoA. Dysfunction of IVD is linked to isovaleric acidemia (IVA), a rare metabolic disorder characterized by the accumulation of toxic metabolites. In this study, we present the cryo-electron microscopy structures of human IVD, resolved both in its apo form and in complex with its substrates, isovaleryl-CoA and butyryl-CoA. Our findings reveal a tetrameric architecture with distinct substrate-binding pockets that facilitate the enzyme's preference for short branched-chain acyl-CoAs. Key residues involved in FAD binding and substrate interaction were identified, elucidating the catalytic mechanism of IVD. Additionally, we investigated the impact of v","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025","modification":"2026-05-29T16:52:35.387Z","creation":"2026-04-08T05:27:38.446Z"},"accession":"S-EPMC12369846","cross_references":{"pubmed":["40851894"],"doi":["10.34133/research.0661"]}}