{"doi":"10.1074/jbc.m112.369116","title":"A Low pK Cysteine at the Active Site of Mouse Methionine Sulfoxide Reductase A","abstract":null,"journal":"Journal of Biological Chemistry","year":2012,"id":687464,"datarank":0.5333022092234121,"base_score":3.5553480614894135,"endowment":3.5553480614894135,"self_citation_contribution":0.5333022092234121,"citation_network_contribution":0.0,"self_endowment_contribution":0.5333022092234121,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":34,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":795062,"name":"James M. Gruschus","orcid":"0000-0002-2815-8542","position":1,"is_corresponding":false},{"id":786234,"name":"Geumsoo Kim","orcid":null,"position":2,"is_corresponding":false},{"id":1795934,"name":"Barbara S. Berlett","orcid":null,"position":3,"is_corresponding":false},{"id":465585,"name":"Nico Tjandra","orcid":"0000-0001-6365-5811","position":4,"is_corresponding":false},{"id":337484,"name":"Rodney L. Levine","orcid":"0000-0001-7908-7206","position":5,"is_corresponding":false},{"id":1795932,"name":"Jung Chae Lim","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"A Low pK Cysteine at the Active Site of Mouse Methionine Sulfoxide Reductase A","abstract":"Methionine sulfoxide reductase A is an essential enzyme in the antioxidant system which scavenges reactive oxygen species through cyclic oxidation and reduction of methionine and methionine sulfoxide. Recently it has also been shown to catalyze the reverse reaction, oxidizing methionine residues to methionine sulfoxide. A cysteine at the active site of the enzyme is essential for both reductase and oxidase activities. This cysteine has been reported to have a pK(a) of 9.5 in the absence of substrate, decreasing to 5.7 upon binding of substrate. Using three independent methods, we show that the pK(a) of the active site cysteine of mouse methionine sulfoxide reductase is 7.2 even in the absence of substrate. The primary mechanism by which the pK(a) is lowered is hydrogen bonding of the active site Cys-72 to protonated Glu-115. The low pK(a) renders the active site cysteine susceptible to oxidation to sulfenic acid by micromolar concentrations of hydrogen peroxide. This characteristic supports a role for methionine sulfoxide reductase in redox signaling.","is_dataset_classified":null,"base_score":3.5553480614894135,"endowment":3.5553480614894135,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"22661719","pmcid":"PMC3408155","openalex_id":"https://openalex.org/W2080584906","authors":[],"funders":[{"funder_name":"Intramural NIH HHS","grant_id":"","title":null},{"funder_name":"Intramural NIH HHS","grant_id":"","title":null}],"total_grants":2,"fwci":1.4728,"citation_percentile":0.81193268,"influential_citations":0,"citation_trend":[{"year":2012,"count":1},{"year":2013,"count":6},{"year":2014,"count":3},{"year":2015,"count":2},{"year":2016,"count":4},{"year":2017,"count":3},{"year":2018,"count":2},{"year":2019,"count":2},{"year":2020,"count":3},{"year":2021,"count":1},{"year":2022,"count":2},{"year":2023,"count":3},{"year":2024,"count":1},{"year":2025,"count":1}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"http://www.jbc.org/article/S0021925820737257/pdf","host_type":"journal"},{"url":"http://www.jbc.org/article/S0021925820737257/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925820737257?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925820737257?httpAccept=text/plain","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1074/jbc.M112.369116","host_type":"publisher"},{"url":"https://doi.org/10.1074/jbc.m112.369116","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/22661719","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3408155","host_type":"repository"}],"fields_of_study":["Redox biology and oxidative stress","Sulfur Compounds in Biology","Aldose Reductase and Taurine","Animals","Catalysis","Catalytic Domain","Cysteine","Hydrogen Bonding","Methionine","Methionine Sulfoxide Reductases","Mice","Oxidation-Reduction"],"mesh_terms":["Animals","Catalysis","Cysteine","Hydrogen Bonding","Methionine","Oxidation-Reduction","Catalytic Domain","Methionine Sulfoxide Reductases","Mice"],"keywords":["Methionine sulfoxide","Sulfoxide","Methionine sulfoxide reductase","Methionine","Cysteine","Chemistry","Hydrogen peroxide","MSRA","Active site","Biochemistry","Reductase","Enzyme","Dimethyl sulfoxide","Amino acid","Organic chemistry"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-18T22:02:50.514506Z","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":[]}