{"doi":"10.1021/jacs.5c00453","title":"Stabilization of the Ferryl═Oxoheme Form of <i>Staphylococcus aureus</i> IsdG by Electron Transfer from a Second-Sphere Tryptophan","abstract":"IsdG and IsdI have novel UV/vis absorption spectra that are distinct from those of the three forms of ferryl heme typically found in biological systems: compound I, compound II, and compound ES. In this work, the ferryl heme form of IsdG was characterized because it is an analogue for the immediate product of enzyme-catalyzed heme hydroxylation. The ferryl heme form of IsdG generated following the addition of meta-chloroperoxybenzoic acid to the ferric heme form of IsdG has a half-life of 4.0 ± 0.2 min, which is more than 100 times longer than the half-life for the ferryl heme form of human heme oxygenase (hHO). Magnetic circular dichroism characterization of the IsdG species yielded spectral data and zero-field splitting parameters consistent with either a compound II- or compound ES-like ferryl heme. Further characterization of isotopically enriched samples with electron paramagnetic resonance spectroscopy revealed the presence of a protein-based organic radical, as would be expected for compound ES. Finally, multiscale quantum mechanics/molecular mechanics and time-dependent density functional theory strongly suggest that the ferryl heme form of IsdG has a ruffled porphyrin ligand and an oxo ligand. Thus, the ferryl heme form of IsdG is assigned to a compound ES-like species with a Trp67-based radical. Electron transfer from Trp67 to porphyrin will stabilize the immediate product of heme hydroxylation and provide a thermodynamic driving force for the reaction. Furthermore, the ability to transfer an electron between Trp67 and the substrate may explain the differential reactivity of meso-hydroxyheme in IsdG and hHO.","journal":"Journal of the American Chemical Society","year":2025,"id":540644,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9644,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":829180,"name":"Matthew A. Conger","orcid":"0000-0002-1320-6572","position":1,"is_corresponding":false},{"id":589823,"name":"Matthew D. Liptak","orcid":"0000-0002-4951-6636","position":2,"is_corresponding":false},{"id":1336763,"name":"Aarzoo Grover","orcid":null,"position":0,"is_corresponding":true}],"reference_count":116,"raw_metadata":null,"created_at":"2026-07-19T02:52:38.861025Z","pmid":"40091640","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":[]}