{"doi":"10.1021/acs.biochem.6b00945","title":"Biochemical Analysis of the Lipoprotein Lipase Truncation Variant, LPL<sup>S447X</sup>, Reveals Increased Lipoprotein Uptake","abstract":null,"journal":"Biochemistry","year":2017,"id":592647,"datarank":1.0377536913854584,"base_score":3.295836866004329,"endowment":3.295836866004329,"self_citation_contribution":0.4943755299006494,"citation_network_contribution":0.543378161484809,"self_endowment_contribution":0.4943755299006494,"citer_contribution":0.543378161484809,"corpus_percentile":null,"corpus_rank":null,"citation_count":26,"citer_count":18,"citers_with_citation_signal":18,"citers_with_endowment":18,"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":554624,"name":"Michael J. Lafferty","orcid":"0000-0002-1000-0480","position":1,"is_corresponding":false},{"id":1516606,"name":"Brian J. Eglinger","orcid":null,"position":2,"is_corresponding":false},{"id":578417,"name":"John P. Kane","orcid":"0000-0001-8049-3850","position":3,"is_corresponding":false},{"id":311167,"name":"Saskia B. Neher","orcid":"0000-0003-4165-6674","position":4,"is_corresponding":false},{"id":347607,"name":"Cassandra K. Hayne","orcid":"0000-0002-2485-5949","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Biochemical Analysis of the Lipoprotein Lipase Truncation Variant, LPL<sup>S447X</sup>, Reveals Increased Lipoprotein Uptake","abstract":"Lipoprotein lipase (LPL) is responsible for the hydrolysis of triglycerides from circulating lipoproteins. Whereas most identified mutations in the LPL gene are deleterious, one mutation, LPL S447X, causes a gain of function. This mutation truncates two amino acids from LPL’s C-terminus. Carriers of LPL S447X have decreased VLDL levels and increased HDL levels, a cardioprotective phenotype. LPL S447X is used in Alipogene tiparvovec, the gene therapy product for individuals with familial LPL deficiency. It is unclear why LPL S447X results in a serum lipid profile more favorable than that of LPL. In vitro reports vary as to whether LPL S447X is more active than LPL. We report a comprehensive, biochemical comparison of purified LPL S447X and LPL dimers. We found no difference in specific activity on synthetic and natural substrates. We also did not observe a difference in the K i for ANGPTL4 inhibition of LPL S447X relative to that of LPL. Finally, we analyzed LPL-mediated uptake of fluorescently labeled lipoprotein particles and found that LPL S447X enhanced lipoprotein uptake to a greater degree than LPL did. An LPL structural model suggests that the LPL S447X truncation exposes residues implicated in LPL binding to uptake receptors.","is_dataset_classified":null,"base_score":3.295836866004329,"endowment":3.295836866004329,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"27984852","pmcid":"PMC5848218","openalex_id":"https://openalex.org/W2565906942","authors":[],"funders":[{"funder_name":"National Heart, Lung, and Blood Institute","grant_id":"1 R01 HL125654","title":null},{"funder_name":"American Heart Association","grant_id":"14BGIA20370000","title":null},{"funder_name":"Division of Graduate Education","grant_id":"DGE-11144081","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL125654","title":null},{"funder_name":"Graduate School, University of North Carolina","grant_id":"","title":null}],"total_grants":5,"fwci":1.3634,"citation_percentile":0.84294592,"influential_citations":0,"citation_trend":[{"year":2018,"count":4},{"year":2019,"count":2},{"year":2020,"count":5},{"year":2021,"count":3},{"year":2023,"count":6},{"year":2024,"count":2},{"year":2025,"count":3},{"year":2026,"count":1}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://escholarship.org/content/qt72p6p6ms/qt72p6p6ms.pdf","host_type":"repository"},{"url":"https://escholarship.org/content/qt72p6p6ms/qt72p6p6ms.pdf","host_type":"repository"},{"url":"https://pubs.acs.org/doi/pdf/10.1021/acs.biochem.6b00945","host_type":"publisher"},{"url":"https://escholarship.org/uc/item/72p6p6ms","host_type":"repository"},{"url":"https://doi.org/10.1021/acs.biochem.6b00945","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/27984852","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5848218","host_type":"repository"}],"fields_of_study":["Lipid metabolism and disorders","Diabetes, Cardiovascular Risks, and Lipoproteins","Lipid metabolism and biosynthesis","Angiopoietin-Like Protein 4","Angiopoietins","Animals","Biological Transport","Cholesterol, HDL","Cholesterol, LDL","Cholesterol, VLDL","Gene Expression","Humans","Hyperlipidemias","Lipoprotein Lipase","Mice","Models, Molecular","Mutation","Protein Binding","Protein Domains","Protein Multimerization","Protein Structure, Secondary","Receptors, Lipoprotein","Recombinant Proteins","Serine","Substrate Specificity","Triglycerides"],"mesh_terms":["Protein Domains","Angiopoietin-Like Protein 4","Animals","Biological Transport","Humans","Hyperlipidemias","Lipoprotein Lipase","Cholesterol, HDL","Cholesterol, LDL","Models, Molecular","Mutation","Protein Binding","Recombinant Proteins","Serine","Substrate Specificity","Triglycerides","Cholesterol, VLDL","Gene Expression","Protein Structure, Secondary","Receptors, Lipoprotein","Angiopoietins","Mice","Protein Multimerization"],"keywords":["Lipoprotein lipase","Very low-density lipoprotein","Biochemistry","Chemistry","Lipoprotein","In vitro","Mutation","Biology","Gene","Enzyme","Cholesterol"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-26T14:43:44.900236Z","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":[]}