{"doi":"10.1021/acs.biochem.5c00183","title":"The Fascinating Intricacy of pSer/Thr-Specific Phosphatases and Their Higher-Order Complexes: Emerging Concepts","abstract":null,"journal":"Biochemistry","year":2025,"id":648832,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":1,"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":727091,"name":"Maja Köhn","orcid":"0000-0001-8142-3504","position":1,"is_corresponding":false},{"id":1691160,"name":"Laura Scheinost","orcid":"0009-0008-9023-9862","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The Fascinating Intricacy of pSer/Thr-Specific Phosphatases and Their Higher-Order Complexes: Emerging Concepts","abstract":"The phosphoprotein phosphatase family is responsible for a vast amount of dephosphorylation events on phosphoserine and -threonine in cells. As such, they are involved in key cellular processes, and consequently, disruption of their function contributes to the etiology and progression of diseases. Many of these phosphatases work as holoenzymes, where the catalytic subunit is complexed with regulatory proteins. How these phosphatases are regulated, how they recognize their substrates, and how substrates can be identified are long-standing questions in the field. Here, we lay out recently emerged concepts addressing these questions using examples of the phosphatases PP1, PP2A, and PP5. These new concepts include substrate recruitment through distal complexed proteins, the use of tailored peptide probes and mass spectrometry for substrate identification, substrate recognition through short helical motifs, and insights into holoenzyme assembly, as well as mechanisms of substrate release and phosphatase activation. Furthermore, we discuss future directions enabled by these new insights.","is_dataset_classified":null,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40473240","pmcid":"PMC12178250","openalex_id":"https://openalex.org/W4411050348","authors":[],"funders":[{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"388932620  FOR2743","title":null},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"403222702  SFB1381","title":null},{"funder_name":"H2020 European Research Council","grant_id":"865119","title":"Protein phosphatase 1-disrupting peptides: Scope and mechanism of action in the treatment of heart insufficiency"},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"unidentified","title":"unidentified"}],"total_grants":4,"fwci":0.1865,"citation_percentile":0.40280207,"influential_citations":0,"citation_trend":[{"year":2026,"count":1}],"oa_status":"hybrid","license":"cc-by-nc-nd","oa_locations":[{"url":"https://pubs.acs.org/doi/pdf/10.1021/acs.biochem.5c00183","host_type":"journal"},{"url":"https://pubs.acs.org/doi/pdf/10.1021/acs.biochem.5c00183","host_type":"HYBRID"},{"url":"https://pubs.acs.org/doi/pdf/10.1021/acs.biochem.5c00183","host_type":"publisher"},{"url":"https://doi.org/10.1021/acs.biochem.5c00183","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40473240","host_type":"repository"},{"url":"https://freidok.uni-freiburg.de/data/271886","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12178250/","host_type":"repository"}],"fields_of_study":["Metalloenzymes and iron-sulfur proteins","ATP Synthase and ATPases Research","Enzyme Structure and Function","Medicine","Biology","Chemistry","0301 basic medicine","03 medical and health sciences"],"mesh_terms":["Animals","Humans","Phosphoprotein Phosphatases","Phosphorylation","Phosphoserine","Substrate Specificity","Threonine"],"keywords":["Chemistry","Phosphatase","Order (exchange)","Biochemistry","Computational biology","Biology","Phosphorylation","Threonine","Phosphoserine","Phosphoprotein Phosphatases","Humans","Animals","Substrate Specificity"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Zero hunger"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"pdb"},{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T03:02:02.879800Z","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":[]}