{"doi":"10.1016/j.jinorgbio.2022.112085","title":"Hydroxylation and lyase reactions of steroids catalyzed by mouse cytochrome P450 17A1 (Cyp17a1)","abstract":null,"journal":"Journal of Inorganic Biochemistry","year":2023,"id":48026,"datarank":0.4792846094584423,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.1065486119902422,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.1065486119902422,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":6,"citers_with_citation_signal":3,"citers_with_endowment":3,"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":224998,"name":"Vitchan Kim","orcid":null,"position":1,"is_corresponding":false},{"id":224999,"name":"Gyu-Hyeong Lee","orcid":null,"position":2,"is_corresponding":false},{"id":225000,"name":"Changmin Kim","orcid":null,"position":3,"is_corresponding":false},{"id":225001,"name":"Eunseo Jeong","orcid":null,"position":4,"is_corresponding":false},{"id":225002,"name":"F. Peter Guengerich","orcid":null,"position":5,"is_corresponding":false},{"id":225003,"name":"Donghak Kim","orcid":null,"position":6,"is_corresponding":false},{"id":224997,"name":"Sung-Gyu Lee","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Hydroxylation and lyase reactions of steroids catalyzed by mouse cytochrome P450 17A1 (Cyp17a1)","abstract":"Cytochrome P450 17A1 (CYP17A1) catalyzes 17α-hydroxylation and 17,20-lyase reactions with steroid hormones. Mice contain an orthologous Cyp17a1 enzyme in the genome, and its amino acid sequence has high similarity with human CYP17A1. We purified recombinant mouse Cyp17a1 and characterized its oxidation reactions with progesterone and pregnenolone. The open reading frame of the mouse Cyp17a1 gene was inserted and successfully expressed in Escherichia coli and then purified using Ni<sup>2+</sup>-nitrilotriacetic acid (NTA) affinity column chromatography. Purified mouse Cyp17a1 displayed typical Type I binding titration spectral changes upon the addition of progesterone, 17α-OH progesterone, pregnenolone, and 17α-OH pregnenolone, with similar binding affinities to those of human CYP17A1. Catalytic activities for 17α-hydroxylation and 17,20-lyase reactions were studied using ultra-performance liquid chromatography (UPLC)-mass spectrometry analysis. Mouse Cyp17a1 showed cytochrome b<sub>5</sub> stimulation in catalysis. In comparison to human enzyme, much higher specificity constants (k<sub>cat</sub>/K<sub>m</sub>) were observed with mouse Cyp17a1. In the reactions of Δ4-steroids (progesterone and 17α-OH progesterone), the specificity constants were 2100 times higher than the human enzyme. The addition of cytochrome b<sub>5</sub> produced significant stimulation of 17,20-lyase activities of mouse Cyp17a1. Two Arg mutants of mouse Cyp17a1 (R347H and R358Q) displayed a larger decrease in 17,20-lyase reaction (from 17α-OH pregnenolone to dehydroepiandrosterone, DHEA) than 17α-hydroxylation, indicating that -as in human CYP17A1-these basic residues in mouse Cyp17a1 are important in interacting with the cytochrome b<sub>5</sub> protein in the lyase reactions.","is_dataset_classified":null,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36640554","pmcid":"PMC9892303","openalex_id":"https://openalex.org/W4315476317","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM118122","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01GM118122-21","title":"Metabolism of Carcinogens and Drugs by Human P450s"}],"total_grants":2,"fwci":2.4667,"citation_percentile":0.87194015,"influential_citations":0,"citation_trend":[{"year":2023,"count":3},{"year":2024,"count":4},{"year":2025,"count":2},{"year":2026,"count":2}],"oa_status":"green","license":"Elsevier TDM","oa_locations":[{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9892303/pdf/nihms-1866316.pdf","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9892303","host_type":"GREEN"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9892303/pdf/nihms-1866316.pdf","host_type":"repository"},{"url":"https://api.elsevier.com/content/article/PII:S0162013422003749?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0162013422003749?httpAccept=text/plain","host_type":"publisher"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9892303","host_type":"repository"},{"url":"https://doi.org/10.1016/j.jinorgbio.2022.112085","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/36640554","host_type":"repository"}],"fields_of_study":["Pharmacogenetics and Drug Metabolism","Hormonal and reproductive studies","Estrogen and related hormone effects","Medicine","Chemistry","Biology","0301 basic medicine","0303 health sciences","03 medical and health sciences","Humans","Mice","Animals","Progesterone","Steroid 17-alpha-Hydroxylase","Lyases","Cytochromes b","Hydroxylation","Steroids","Pregnenolone","Catalysis"],"mesh_terms":["Animals","Catalysis","Humans","Hydroxylation","Lyases","Pregnenolone","Progesterone","Steroid 17-alpha-Hydroxylase","Steroids","Cytochromes b","Mice"],"keywords":["CYP17A1","Pregnenolone","Chemistry","Hydroxylation","Biochemistry","Enzyme","Steroid","Progesterone","Enzyme kinetics","enzyme inhibitor","Cytochrome p450","Enzyme Mechanism","Enzyme Catalysis","Cytochrome B(5)","Steroid 17-alpha-Hydroxylase","Lyases","Cytochromes b","Catalysis","Mice","Humans","Animals","Steroids"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. Good health"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-18T20:23:00.224877Z","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":[]}