{"doi":"10.1073/pnas.2102953118","title":"Lipoprotein-associated phospholipase A <sub>2</sub> : A paradigm for allosteric regulation by membranes","abstract":"Significance Lp-PLA 2 is a physiologically important human enzyme and an inflammatory biomarker for assessing risk factors associated with cardiovascular diseases. It is associated with low- and high-density lipoproteins in human plasma and acts on the outside of the phospholipid monolayer that coats these particles, in stark contrast to traditional PLA 2 enzymes that act on bilayer membranes. This study addresses the allosteric activation of Lp-PLA 2 by phospholipid monolayers and membranes, its precise selectivity and specificity for particular oxidized and short acyl-chain phospholipid substrates not previously possible. Of particular importance, this work identifies and confirms by site-directed mutagenesis a phospholipid head-group binding pocket distinct from known drug inhibitor binding pockets that informs us about Lp-PLA 2 ’s mechanism of action and creates opportunities for additional therapeutic approaches.","journal":"Proceedings of the National Academy of Sciences","year":2022,"id":243253,"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":34,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9631,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":515989,"name":"Daiki Hayashi","orcid":"0000-0002-2616-448X","position":1,"is_corresponding":false},{"id":637701,"name":"Alexis M. Vasquez","orcid":null,"position":2,"is_corresponding":false},{"id":875000,"name":"Jian Cao","orcid":"0000-0002-8825-662X","position":3,"is_corresponding":false},{"id":71092,"name":"J. Andrew McCammon","orcid":"0000-0003-3065-1456","position":4,"is_corresponding":false},{"id":108033,"name":"Edward A. Dennis","orcid":"0000-0003-3738-3140","position":5,"is_corresponding":false},{"id":515990,"name":"Varnavas D. Mouchlis","orcid":"0000-0002-4235-1867","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-19T00:23:16.032700Z","pmid":"34996868","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":[]}