{"doi":"10.52843/cassyni.tq4xcn","title":"20th international Biometals Webinars","abstract":"26th international Biometals Webinars Noncanonical peroxide stress response regulation in bacteria by the hydrogen peroxide-sensing metalloprotein PexR Redox processes are essential in all aerobic organisms, but they involve the formation of reactive oxygen species, such as hydrogen peroxide (H₂O₂), which cause oxidative stress when they exceed physiological levels. Cells combat H₂O₂ through peroxiredoxins and catalases, whose expression in bacteria is usually controlled by OxyR or PerR. The study of how a soil bacterium responds to H₂O₂ has revealed a novel regulatory mechanism, dependent on PexR, a \"bacterial enhancer binding protein\" widely spread among myxobacteria, which possibly also operates in other bacteria. The work, published in Nucleic Acids Research, has been carried out by Eva Bastida and Irene del Rey, under the direction of Profs. Montserrat Elías-Arnanz (University of Murcia) and S. Padmanabhan (IQF-CSIC, Madrid), with the collaboration of Prof. Catherine Drennan (MIT, USA) and Naike Ye. Through genetic, transcriptomic, biochemical and structural analyses, it has been shown that PexR binds ATP, forms oligomers and exerts a dual regulation essential for cell viability. Without H₂O₂ stress, PexR represses the expression of a peroxiredoxin from a promoter dependent on the primary sigma factor. H₂O₂ causes the expulsion of the metal attached to the N-terminal domain of PexR, freeing it from autoinhibition by this module and allowing it to activate the expression of a peroxiredoxin and a catalase, from promoters that are dependent on the alternative sigma54 factor. PexR exemplifies a H₂O₂ response mechanism beyond established paradigms and expands the toolkit for generating H₂O₂ biosensors. The superoxide dismutases as a model for studying metalloprotein evolution It is estimated that around one-third of all proteins in nature require an essential metal cofactor to function. This abundance of metalloproteins makes the understanding of the molecular mechanisms that determine the selectivity and specificity of metal-protein interactions relevant to every aspect of modern biology, medicine and biotechnology. Most metalloproteins exhibit cofactor specificity, possessing reduced, or even abrogated activity when associated with the ‘wrong’ metal cofactor in vitro and in vivo. We are studying a ubiquitous family of metal-dependent enzymes, the manganese/iron-dependent superoxide dismutases (SODs), to interrogate how cofactor specificity is controlled by the protein architecture and how such specificity evolves. Published data will be described that demonstrate how a pair of closely related SODs from Staphylococcus aureus have evolved different metal specificities that enable this pathogen to circumvent host-imposed manganese starvation that it experiences during infection. The value of this unique SOD pair as a model system with which to study the fundamental mechanisms by which proteins regulate the reactivity of their metal cofactor to give rise to specificity will be demonstrated. Data will then be presented showing that the ubiquitous SODs can be leveraged through bioinformatic, biochemical and structural studies to study how evolution can adjust metal specificity over time, giving rise to distinct enzymes with varying metal usage adapted to the metal availability experienced in its host’s niche.","journal":null,"year":2025,"id":580008,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9506,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"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":568986,"name":"Gabriele Meloni","orcid":"0000-0003-4976-1401","position":1,"is_corresponding":false},{"id":877436,"name":"Raphaël Rodriguez","orcid":"0000-0001-7668-446X","position":2,"is_corresponding":false},{"id":1339745,"name":"Isabelle Michaud‐Soret","orcid":"0000-0002-8936-4964","position":0,"is_corresponding":true}],"reference_count":2,"raw_metadata":null,"created_at":"2026-07-19T02:58:34.718602Z","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":[]}