{"doi":"10.1074/jbc.m401868200","title":"Narrow Substrate Specificity and Sensitivity toward Ligand-binding Site Mutations of Human T-cell Leukemia Virus Type 1 Protease","abstract":null,"journal":"Journal of Biological Chemistry","year":2004,"id":627263,"datarank":0.5837730447165941,"base_score":3.8918202981106265,"endowment":3.8918202981106265,"self_citation_contribution":0.5837730447165941,"citation_network_contribution":0.0,"self_endowment_contribution":0.5837730447165941,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":48,"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":484834,"name":"Irene T. Weber","orcid":"0000-0003-4876-7393","position":1,"is_corresponding":false},{"id":1623393,"name":"Péter Bagossi","orcid":null,"position":2,"is_corresponding":false},{"id":909799,"name":"Gabriella Miklóssy","orcid":null,"position":3,"is_corresponding":false},{"id":869168,"name":"Péter Boross","orcid":null,"position":4,"is_corresponding":false},{"id":177185,"name":"Stephen Oroszlan","orcid":null,"position":5,"is_corresponding":false},{"id":1623398,"name":"József Tözsér","orcid":null,"position":6,"is_corresponding":false},{"id":1623390,"name":"János Kádas","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Narrow Substrate Specificity and Sensitivity toward Ligand-binding Site Mutations of Human T-cell Leukemia Virus Type 1 Protease","abstract":"Human T-cell leukemia virus type 1 (HTLV-1) is associated with a number of human diseases; therefore, its protease is a potential target for chemotherapy. To compare the specificity of HTLV-1 protease with that of human immunodeficiency virus type 1 (HIV-1) protease, oligopeptides representing naturally occurring cleavage sites in various retroviruses were tested. The number of hydrolyzed peptides as well as the specificity constants suggested a substantially broader specificity of the HIV protease. Amino acid residues of HTLV-1 protease substrate-binding sites were replaced by equivalent ones of HIV-1 protease. Most of the single and multiple mutants had altered specificity and a dramatically reduced folding and catalytic capability, suggesting that mutations are not well tolerated in HTLV-1 protease. The catalytically most efficient mutant was that with the flap residues of HIV-1 protease. The inhibition profile of the mutants was also determined for five inhibitors used in clinical practice and inhibitor analogs of HTLV-1 cleavage sites. Except for indinavir, the HIV-1 protease inhibitors did not inhibit wild type and most of the mutant HTLV-1 proteases. The wild type HTLV-1 protease was inhibited by the reduced peptide bond-containing substrate analogs, whereas the mutants showed various degrees of weakened binding capability. Most interesting, the enzyme with HIV-1-like residues in the flap region was the most sensitive to the HIV-1 protease inhibitors and least sensitive to the HTLV-1 protease inhibitors, indicating that the flap plays an important role in defining the specificity differences of retroviral proteases.","is_dataset_classified":null,"base_score":3.8918202981106265,"endowment":3.8918202981106265,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"15102858","pmcid":null,"openalex_id":"https://openalex.org/W2038661428","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM062920","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"GM62920","title":null},{"funder_name":"FIC NIH HHS","grant_id":"TW01001","title":null}],"total_grants":3,"fwci":1.0141,"citation_percentile":0.74407347,"influential_citations":0,"citation_trend":[{"year":2012,"count":2},{"year":2013,"count":1},{"year":2014,"count":4},{"year":2015,"count":2},{"year":2016,"count":1},{"year":2017,"count":1},{"year":2019,"count":1},{"year":2020,"count":1},{"year":2021,"count":7},{"year":2022,"count":1},{"year":2023,"count":1},{"year":2026,"count":1}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"http://www.jbc.org/article/S0021925820853721/pdf","host_type":"journal"},{"url":"http://www.jbc.org/article/S0021925820853721/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925820853721?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925820853721?httpAccept=text/plain","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1074/jbc.M401868200","host_type":"publisher"},{"url":"https://doi.org/10.1074/jbc.m401868200","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/15102858","host_type":"repository"},{"url":"http://hdl.handle.net/2437/156694","host_type":"repository"},{"url":"http://www.jbc.org/content/279/26/27148.full.pdf","host_type":"Unpaywall"}],"fields_of_study":["T-cell and Retrovirus Studies","Animal Disease Management and Epidemiology","Vector-Borne Animal Diseases"],"mesh_terms":["Amino Acid Sequence","Binding Sites","Humans","Kinetics","Ligands","Models, Molecular","Molecular Sequence Data","Oligopeptides","Protease Inhibitors","Recombinant Fusion Proteins","Substrate Specificity","Human T-lymphotropic virus 1","HIV-1","Aspartic Acid Endopeptidases","Mutagenesis, Site-Directed","HIV Protease","Nucleocapsid"],"keywords":["Protease","NS2-3 protease","Proteases","Mutant","HIV-1 protease","Indinavir","Biology","MASP1","Cleavage (geology)","Biochemistry","Enzyme","Molecular biology","Wild type","Binding site","Virology","Virus","Chemistry","Serine protease","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-04T16:51:54.904519Z","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":[]}