{"doi":"10.1093/nar/gkaf328","title":"Unexpected enzymatic function of an ancient nucleic acid-binding fold","abstract":"Aminoacyl-tRNA synthetases (ARSs) are indispensable for all living organisms and their associated aminoacyl-tRNA editing domains ensure the fidelity of translation. In eukaryotes, ARSs form a multi-aminoacyl-tRNA synthetase complex (MSC), which is assembled together with several nonsynthetase scaffolding proteins. The MSC found in Trypanosoma brucei (Tb) includes two proteins with oligosaccharide/oligonucleotide-binding (OB) folds-MSC-associated protein 1 (MCP1) and MCP2-and one known trans-editing factor, MCP3, an Ala-tRNA deacylase. The activity of MCP1 was unexplored until now. Our study shows that recombinantly-expressed and purified MCP1 also deacylates Ala-tRNAs despite lacking known tRNA-editing domain homology. Domain deletion studies reveal that the OB-fold houses the catalytic pocket and mutation of any one of three conserved OB-fold residues (K326, R331, S335) abolishes activity. Assays with Saccharomyces cerevisiae Arc1p reveal that MCP1's deacylation activity is conserved across organisms. This discovery explains the 3' CCA-end binding activity of this protein family and uncovers an ancient nucleic acid binding domain's unexpected enzymatic function.","journal":"Nucleic Acids Research","year":2025,"id":543905,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9635,"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":1434206,"name":"Stella Bockelman","orcid":null,"position":1,"is_corresponding":false},{"id":1302106,"name":"Anna Vradi","orcid":null,"position":2,"is_corresponding":false},{"id":1434207,"name":"Kaylee Grabarkewitz","orcid":null,"position":3,"is_corresponding":false},{"id":1434208,"name":"Alexa Pyun","orcid":null,"position":4,"is_corresponding":false},{"id":1433826,"name":"J. C. Stark","orcid":"0009-0007-7828-9966","position":5,"is_corresponding":false},{"id":242368,"name":"Vicki H. Wysocki","orcid":"0000-0003-0495-2538","position":6,"is_corresponding":false},{"id":273315,"name":"Juan Alfonzo","orcid":"0000-0002-8503-3316","position":7,"is_corresponding":false},{"id":1433827,"name":"Karin Musier-Forsyth","orcid":"0000-0002-0354-4172","position":8,"is_corresponding":false},{"id":1434205,"name":"Rylan R Watkins","orcid":null,"position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T02:53:08.338070Z","pmid":"40274265","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":[]}