{"doi":"10.3390/ijms21218367","title":"The Convergence of the Hedgehog/Intein Fold in Different Protein Splicing Mechanisms","abstract":"Protein splicing catalyzed by inteins utilizes many different combinations of amino-acid types at active sites. Inteins have been classified into three classes based on their characteristic sequences. We investigated the structural basis of the protein splicing mechanism of class 3 inteins by determining crystal structures of variants of a class 3 intein from Mycobacterium chimaera and molecular dynamics simulations, which suggested that the class 3 intein utilizes a different splicing mechanism from that of class 1 and 2 inteins. The class 3 intein uses a bond cleavage strategy reminiscent of proteases but share the same Hedgehog/INTein (HINT) fold of other intein classes. Engineering of class 3 inteins from a class 1 intein indicated that a class 3 intein would unlikely evolve directly from a class 1 or 2 intein. The HINT fold appears as structural and functional solution for trans-peptidyl and trans-esterification reactions commonly exploited by diverse mechanisms using different combinations of amino-acid types for the active-site residues.","journal":"International Journal of Molecular Sciences","year":2020,"id":113793,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9475,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":536492,"name":"Salla Virtanen","orcid":"0000-0002-7965-6066","position":1,"is_corresponding":false},{"id":536493,"name":"A. Sesilja Aranko","orcid":"0000-0001-9425-3524","position":2,"is_corresponding":false},{"id":537154,"name":"Kornelia M. Mikula","orcid":null,"position":3,"is_corresponding":false},{"id":536494,"name":"G.T. Lountos","orcid":"0000-0003-3463-8881","position":4,"is_corresponding":false},{"id":376430,"name":"Alexander Wlodawer","orcid":"0000-0002-5510-9703","position":5,"is_corresponding":false},{"id":536495,"name":"O. H. Samuli Ollila","orcid":"0000-0002-8728-1006","position":6,"is_corresponding":false},{"id":536496,"name":"Hideo Iwaï","orcid":"0000-0001-7376-5264","position":7,"is_corresponding":false},{"id":536491,"name":"Hannes M. Beyer","orcid":"0000-0002-6882-006X","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-18T23:13:25.964732Z","pmid":"33171880","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":[]}