{"doi":"10.1016/j.jbc.2025.110477","title":"Hemoglobin β-F41K: A recombinant oxygen carrier prototype engineered for enhanced heme retention, stability, and optimal oxygenation properties","abstract":"Recombinant hemoglobin-based oxygen carriers (rHBOCs) have several potential advantages as blood substitutes in transfusion medicine, especially in emergency situations. However, the wide use of rHBOCs in humans has been limited by challenges including hypertension due to nitric oxide scavenging, autoregulatory responses, and rapid heme dissociation. Among these, heme dissociation remains a critical unresolved issue, as it leads to toxicity and compromises oxygen delivery efficiency. Heme retention in the globin moiety is a key problem that needs to be solved to develop recombinant HBOCs as safe transfusion agents. Here, we report the results of protein engineering experiments to enhance heme retention and thermal stability with the aim of designing stable HBOCs. We successfully introduced a mutation into recombinant human Hb0.1 (rHb0.1), named β-F41K, that significantly reduced rates of heme dissociation and auto-oxidation while simultaneously maintaining thermal stability and oxygen affinity at levels well suited to respiratory gas transport in vivo. The higher rate of heme retention in recombinant Hb0.1 β-F41K makes this protein an especially promising HBOC prototype.","journal":"Journal of Biological Chemistry","year":2025,"id":521623,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9528,"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":1392483,"name":"Kajal Yadav","orcid":null,"position":1,"is_corresponding":false},{"id":459423,"name":"Anthony V. Signore","orcid":"0000-0002-0664-0864","position":2,"is_corresponding":false},{"id":1392484,"name":"Nidhi Mittal","orcid":null,"position":3,"is_corresponding":false},{"id":392743,"name":"Sheetal Uppal","orcid":"0000-0002-3685-8602","position":4,"is_corresponding":false},{"id":1391972,"name":"Amit Kumar Tyagi","orcid":"0000-0002-1187-8332","position":5,"is_corresponding":false},{"id":1391973,"name":"Gaurav Mittal","orcid":"0000-0001-6898-522X","position":6,"is_corresponding":false},{"id":272499,"name":"Jay F. Storz","orcid":"0000-0001-5448-7924","position":7,"is_corresponding":false},{"id":1011501,"name":"Suman Kundu","orcid":"0000-0002-8960-2096","position":8,"is_corresponding":false},{"id":1118062,"name":"Mohd Asim Khan","orcid":"0000-0002-4698-2332","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T02:49:44.558743Z","pmid":"40653198","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":[]}