{"doi":"10.1126/science.abc5667","title":"Structural basis of antagonizing the vitamin K catalytic cycle for anticoagulation","abstract":"Vitamin K antagonists are widely used anticoagulants that target vitamin K epoxide reductases (VKOR), a family of integral membrane enzymes. To elucidate their catalytic cycle and inhibitory mechanism, we report 11 x-ray crystal structures of human VKOR and pufferfish VKOR-like, with substrates and antagonists in different redox states. Substrates entering the active site in a partially oxidized state form cysteine adducts that induce an open-to-closed conformational change, triggering reduction. Binding and catalysis are facilitated by hydrogen-bonding interactions in a hydrophobic pocket. The antagonists bind specifically to the same hydrogen-bonding residues and induce a similar closed conformation. Thus, vitamin K antagonists act through mimicking the key interactions and conformational changes required for the VKOR catalytic cycle.","journal":"Science","year":2020,"id":57201,"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":80,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9601,"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":298408,"name":"Shuang Li","orcid":"0000-0002-8930-4072","position":1,"is_corresponding":false},{"id":298409,"name":"Guomin Shen","orcid":"0000-0002-5006-2790","position":2,"is_corresponding":false},{"id":298410,"name":"N. Sukumar","orcid":"0000-0002-3149-9292","position":3,"is_corresponding":false},{"id":298411,"name":"Andrzej M. Krezel","orcid":"0000-0003-3246-5008","position":4,"is_corresponding":false},{"id":298412,"name":"Weikai Li","orcid":"0000-0002-8711-1904","position":5,"is_corresponding":false},{"id":298407,"name":"Shixuan Liu","orcid":"0000-0003-3886-144X","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-18T21:06:31.136481Z","pmid":"33154105","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":[]}