{"doi":"10.1021/jacs.3c07450","title":"Experimental Evidence and Mechanistic Description of the Phenolic H-Transfer to the Cu<sub>2</sub>O<sub>2</sub> Active Site of oxy-Tyrosinase","abstract":"Tyrosinase is a ubiquitous coupled binuclear copper enzyme that activates O 2 toward the regioselective monooxygenation of monophenols to catechols via a mechanism that remains only partially defined. Here, we present new mechanistic insights into the initial steps of this monooxygenation reaction by employing a pre-steady-state, stopped-flow kinetics approach that allows for the direct measurement of the monooxygenation rates for a series of para -substituted monophenols by oxy-tyrosinase. The obtained biphasic Hammett plot and the associated solvent kinetic isotope effect values provide direct evidence for an initial H-transfer from the protonated phenolic substrate to the Cu 2 O 2 core of oxy-tyrosinase. The correlation of these experimental results to quantum mechanics/molecular mechanics calculations provides a detailed mechanistic description of this H-transfer step. These new mechanistic insights revise and expand our fundamental understanding of Cu 2 O 2 active sites in biology.","journal":"Journal of the American Chemical Society","year":2023,"id":336620,"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":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9465,"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":863511,"name":"Agnieszka Stańczak","orcid":"0000-0002-5335-1387","position":1,"is_corresponding":false},{"id":1067454,"name":"Eleanor M. Dunietz","orcid":"0009-0005-0544-3825","position":2,"is_corresponding":false},{"id":864105,"name":"Jake W. Ginsbach","orcid":null,"position":3,"is_corresponding":false},{"id":337365,"name":"Martin Srnec","orcid":"0000-0001-5118-141X","position":4,"is_corresponding":false},{"id":337364,"name":"Lubomı́r Rulı́šek","orcid":"0000-0002-7769-7059","position":5,"is_corresponding":false},{"id":271050,"name":"Edward I. Solomon","orcid":"0000-0003-0291-3199","position":6,"is_corresponding":false},{"id":863510,"name":"Ioannis Kipouros","orcid":"0000-0002-0404-5615","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":null,"created_at":"2026-07-19T01:10:21.947540Z","pmid":"37844210","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":[]}