{"doi":"10.1002/bio.4415","title":"Copper‐mediated oxidation of imidazopyrazinones inhibits marine luciferase activity","abstract":"<jats:title>Abstract</jats:title><jats:p>The development of bioluminescence‐based tools has seen steady growth in the field of chemical biology over the past few decades ranging in uses from reporter genes to assay development and targeted imaging. More recently, coelenterazine‐utilizing luciferases such as <jats:italic>Gaussia</jats:italic>, <jats:italic>Renilla</jats:italic>, and the engineered nano‐luciferases have been utilized due to their intense luminescence relative to firefly luciferin/luciferase. The emerging importance of these systems warrants investigations into the components that affect their light production. Previous work has reported that one marine luciferase<jats:italic>, Gaussia</jats:italic>, is potently inhibited by copper salt. The mechanism for inhibition was not elucidated but was hypothesized to occur via binding to the enzyme. In this study, we provide the first report of a group of nonhomologous marine luciferases also exhibiting marked decreases in light emission in the presence of copper (II). We investigate the mechanism of action behind this inhibition and demonstrate that the observed copper inhibition does not stem from a luciferase interaction but rather the chemical oxidation of imidazopyrazinone luciferins generating inert, dehydrated luciferins.</jats:p>","journal":"Luminescence","year":2023,"id":22324,"datarank":0.32191573553487685,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.05315181515066857,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.05315181515066857,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":5,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":140717,"name":"Vanessa J. 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O'Sullivan","orcid":"0000-0003-0264-7783","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":1.791759469228055,"endowment":1.791759469228055,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36409206","pmcid":"PMC10281456","openalex_id":"https://openalex.org/W4309511335","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"NIH MIRA 5R35GM133684‐02","title":null},{"funder_name":"National Institutes of Health","grant_id":"NIH DK104770","title":null},{"funder_name":"National Science Foundation","grant_id":"NSF CAREER 2048265","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R35 GM133684","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK104770","title":null},{"funder_name":"National Science Foundation","grant_id":"2048265","title":"CAREER: Elucidating the Interaction Dynamics of Soil Metals with Flavonoids in the Plant Rhizosphere"},{"funder_name":"National Institutes of Health","grant_id":"5R35GM133684-02","title":"Metalloendocrinology: Mapping Bioinorganic Chemistry in the Extracellular Space"},{"funder_name":"National Institutes of Health","grant_id":"5R01DK104770-03","title":"Epigenetic regulation of Wilson Disease"}],"total_grants":8,"fwci":0.4331,"citation_percentile":0.59569644,"influential_citations":0,"citation_trend":[{"year":2023,"count":1},{"year":2024,"count":2},{"year":2025,"count":2}],"oa_status":"green","license":"Wiley Online Library User Agreement","oa_locations":[{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10281456/pdf/nihms-1900867.pdf","host_type":"repository"},{"url":"https://rss.onlinelibrary.wiley.com/doi/am-pdf/10.1002/bio.4415","host_type":"BRONZE"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10281456/pdf/nihms-1900867.pdf","host_type":"repository"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/bio.4415","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1002/bio.4415","host_type":"publisher"},{"url":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/am-pdf/10.1002/bio.4415","host_type":"publisher"},{"url":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/pdf/10.1002/bio.4415","host_type":"publisher"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10281456","host_type":"repository"},{"url":"https://doi.org/10.1002/bio.4415","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/36409206","host_type":"repository"}],"fields_of_study":["bioluminescence and chemiluminescence research","Photoreceptor and optogenetics research","Molecular Communication and Nanonetworks","Medicine","Chemistry","01 natural sciences","0104 chemical sciences","Copper","Luciferases","Oxidation-Reduction","Luciferases, Firefly","Firefly Luciferin","Luminescent Measurements","Luminescence"],"mesh_terms":["Copper","Luciferases","Luminescent Measurements","Oxidation-Reduction","Luciferases, Firefly","Luminescence","Firefly Luciferin"],"keywords":["Luciferases","Luciferase","Bioluminescence","Luciferin","Chemistry","Biophysics","Biochemistry","Biology","Gene","Transfection","Copper","Imidazopyrazinone","Marine Luciferin","Marine Luciferase","Luminescence","Luciferases, Firefly","Luminescent Measurements","Firefly Luciferin","Oxidation-Reduction"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life below water"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-06T19:15:59.463830Z","pmid":null,"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":[]}