{"doi":"10.3390/ijms24054555","title":"Probing the E1o-E2o and E1a-E2o Interactions in Binary Subcomplexes of the Human 2-Oxoglutarate Dehydrogenase and 2-Oxoadipate Dehydrogenase Complexes by Chemical Cross-Linking Mass Spectrometry and Molecular Dynamics Simulation","abstract":"The human 2-oxoglutarate dehydrogenase complex (hOGDHc) is a key enzyme in the tricarboxylic acid cycle and is one of the main regulators of mitochondrial metabolism through NADH and reactive oxygen species levels. Evidence was obtained for formation of a hybrid complex between the hOGDHc and its homologue the 2-oxoadipate dehydrogenase complex (hOADHc) in the L-lysine metabolic pathway, suggesting a crosstalk between the two distinct pathways. Findings raised fundamental questions about the assembly of hE1a (2-oxoadipate-dependent E1 component) and hE1o (2-oxoglutarate-dependent E1) to the common hE2o core component. Here we report chemical cross-linking mass spectrometry (CL-MS) and molecular dynamics (MD) simulation analyses to understand assembly in binary subcomplexes. The CL-MS studies revealed the most prominent loci for hE1o-hE2o and hE1a-hE2o interactions and suggested different binding modes. The MD simulation studies led to the following conclusions: (i) The N-terminal regions in E1s are shielded by, but do not interact directly with hE2o. (ii) The hE2o linker region exhibits the highest number of H-bonds with the N-terminus and α/β1 helix of hE1o, yet with the interdomain linker and α/β1 helix of hE1a. (iii) The C-termini are involved in dynamic interactions in complexes, suggesting the presence of at least two conformations in solution.","journal":"International Journal of Molecular Sciences","year":2023,"id":359091,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9549,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":447173,"name":"Xu Zhang","orcid":"0000-0002-8103-8486","position":1,"is_corresponding":false},{"id":365815,"name":"Natalia S. Nemeria","orcid":null,"position":2,"is_corresponding":false},{"id":364840,"name":"Attila Ambrus","orcid":"0000-0001-6014-3175","position":3,"is_corresponding":false},{"id":364838,"name":"Frank Jordan","orcid":"0000-0003-1354-718X","position":4,"is_corresponding":false},{"id":447176,"name":"Olivér Ozohanics","orcid":"0000-0002-2705-9921","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T01:13:52.889556Z","pmid":"36901986","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}