{"doi":"10.1101/2024.09.19.613983","title":"Dynamic metal coordination controls chemoselectivity in radical halogenases","abstract":"Abstract The activation of inert C( sp 3 )-H bonds by non-heme Fe enzymes plays a key role in metabolism, epigenetics, and signaling, while providing a powerful biocatalytic platform for the chemical synthesis of molecules with increased sp 3 complexity. In this context, Fe II /α-ketoglutarate-dependent radical halogenases represent a broadly interesting system, as they are uniquely capable of carrying out transfer of a diverse array of bound anions following C-H activation. Here, we provide the first experimental evidence that bifurcation of H-atom abstraction and radical rebound is driven both by the ability of a dynamic metal coordination sphere to reorganize as well as by a second-sphere hydrogen-bond network where only two residues (Asn224 and Ile151) are necessary and sufficient. The identification of this minimal motif provides a paradigm for understanding the evolution of catalytic plasticity in these enzymes and yields new insight into the design principles by which to expand their reaction scope.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":486361,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":863510,"name":"Ioannis Kipouros","orcid":"0000-0002-0404-5615","position":1,"is_corresponding":false},{"id":823382,"name":"Jeffrey W. Slater","orcid":"0000-0002-1126-8905","position":2,"is_corresponding":false},{"id":378490,"name":"Elizabeth A. Stone","orcid":"0000-0002-2253-3452","position":3,"is_corresponding":false},{"id":1329775,"name":"A. Yang","orcid":"0000-0003-1503-4070","position":4,"is_corresponding":false},{"id":665151,"name":"Augustin Braun","orcid":"0000-0002-9487-5769","position":5,"is_corresponding":false},{"id":1329776,"name":"Alder R. Ensberg","orcid":"0009-0009-1389-5863","position":6,"is_corresponding":false},{"id":1329777,"name":"Andrew M. Whitten","orcid":"0000-0002-7968-6433","position":7,"is_corresponding":false},{"id":1329778,"name":"Kuntal Chatterjee","orcid":"0000-0001-6984-5026","position":8,"is_corresponding":false},{"id":240873,"name":"Isabel Bogacz","orcid":"0000-0003-1493-3867","position":9,"is_corresponding":false},{"id":240893,"name":"Junko Yano","orcid":"0000-0001-6308-9071","position":10,"is_corresponding":false},{"id":304951,"name":"J. Martin Bollinger","orcid":"0000-0003-0751-8585","position":11,"is_corresponding":false},{"id":1005692,"name":"Michelle C. Y. Chang","orcid":"0000-0002-9034-1540","position":12,"is_corresponding":false},{"id":284971,"name":"Elijah N. Kissman","orcid":"0000-0002-3278-8010","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T02:07:57.049469Z","pmid":"39345585","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":[]}