{"doi":"10.1039/d0sc06369j","title":"A novel catalytic heme cofactor in SfmD with a single thioether bond and a <i>bis</i> -His ligand set revealed by a <i>de novo</i> crystal structural and spectroscopic study","abstract":", His274 and His313. We demonstrated that SfmD heme is catalytically active and can utilize dioxygen and ascorbate for a single-oxygen insertion into 3-methyl-l-tyrosine. Catalytic assays using ascorbate derivatives revealed the functional groups of ascorbate essential to its function as a cosubstrate. Abolishing the thioether linkage through mutation of Cys317 resulted in catalytically inactive SfmD variants. EPR and optical data revealed that the heme center undergoes a substantial conformational change with one axial histidine ligand dissociating from the iron ion in response to substrate 3-methyl-l-tyrosine binding or chemical reduction by a reducing agent, such as the cosubstrate ascorbate. The labile axial ligand was identified as His274 through redox-linked structural determinations. Together, identifying an unusual heme cofactor with a previously unknown heme-binding motif for a monooxygenase activity and the structural similarity of SfmD to the members of the heme-based tryptophan dioxygenase superfamily will broaden understanding of heme chemistry.","journal":"Chemical Science","year":2021,"id":179136,"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":18,"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":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":59246,"name":"Ian Davis","orcid":"0000-0002-1566-4972","position":1,"is_corresponding":false},{"id":726581,"name":"Karinel Nieves-Merced","orcid":null,"position":2,"is_corresponding":false},{"id":333657,"name":"Yifan Wang","orcid":"0000-0003-0378-2469","position":3,"is_corresponding":false},{"id":396030,"name":"Stanton F. McHardy","orcid":"0000-0003-0070-4924","position":4,"is_corresponding":false},{"id":333661,"name":"Aimin Liu","orcid":"0000-0002-4182-8176","position":5,"is_corresponding":false},{"id":725872,"name":"Inchul Shin","orcid":"0000-0001-8111-8948","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":null,"created_at":"2026-07-18T23:47:44.875897Z","pmid":"34163669","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":[]}