{"doi":"10.1002/anie.202407018","title":"Indole <i>N</i> ‐Linked Hydroperoxyl Adduct of Protein‐Derived Cofactor Modulating Catalase‐Peroxidase Functions","abstract":"Bifunctional catalase-peroxidase (KatG) features a posttranslational methionine-tyrosine-tryptophan (MYW) crosslinked cofactor crucial for its catalase function, enabling pathogens to neutralize hydrogen peroxide during infection. We discovered the presence of indole nitrogen-linked hydroperoxyl adduct (MYW-OOH) in Mycobacterium tuberculosis KatG in the solution state under ambient conditions, suggesting its natural occurrence. By isolating predominantly MYW-OOH-containing KatG protein, we investigated the chemical stability and functional impact of MYW-OOH. We discovered that MYW-OOH inhibits catalase activity, presenting a unique temporary lock. Exposure to peroxide or increased temperature removes the hydroperoxyl adduct from the protein cofactor, converting MYW-OOH to MYW and restoring the detoxifying ability of the enzyme against hydrogen peroxide. Thus, the N-linked hydroperoxyl group is releasable. KatG with MYW-OOH represents a catalase dormant, but primed, state of the enzyme. These findings provide insight into chemical strategies targeting the bifunctional enzyme KatG in pathogens, highlighting the role of N-linked hydroperoxyl modifications in enzymatic function.","journal":"Angewandte Chemie International Edition","year":2024,"id":469242,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9531,"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":1221624,"name":"Ran Duan","orcid":"0000-0002-5370-5990","position":1,"is_corresponding":false},{"id":774623,"name":"Ephrahime S. Traore","orcid":"0000-0001-6419-9248","position":2,"is_corresponding":false},{"id":1056332,"name":"Romie C. Nguyen","orcid":"0000-0002-9450-2364","position":3,"is_corresponding":false},{"id":59246,"name":"Ian Davis","orcid":"0000-0002-1566-4972","position":4,"is_corresponding":false},{"id":1302982,"name":"Wendell P. Griffth","orcid":null,"position":5,"is_corresponding":false},{"id":1302608,"name":"Douglas C. Goodwin","orcid":"0000-0002-7869-7704","position":6,"is_corresponding":false},{"id":1302609,"name":"Andrzej A. Jarzęcki","orcid":"0000-0002-8737-2354","position":7,"is_corresponding":false},{"id":333661,"name":"Aimin Liu","orcid":"0000-0002-4182-8176","position":8,"is_corresponding":false},{"id":774624,"name":"Jiasong Li","orcid":"0000-0003-0341-2038","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-19T02:05:28.027781Z","pmid":"39300819","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":[]}