{"doi":"10.1002/1873-3468.13191","title":"Crystal structure of plasma kallikrein reveals the unusual flexibility of the S1 pocket triggered by Glu217","abstract":"<jats:sec><jats:label/><jats:p>Serine proteases play important roles in numerous physiological and pathophysiological processes. Moreover, serine proteases are classical subjects for studies of catalytic and inhibitory mechanisms of enzymes. Here, we determined the crystal structures of a serine protease, murine plasma kallikrein (<jats:styled-content style=\"fixed-case\">mPK</jats:styled-content>), and its complex with a peptidic inhibitor. Although <jats:styled-content style=\"fixed-case\">mPK</jats:styled-content> in the complex adopts a canonical protease structure, the apo‐<jats:styled-content style=\"fixed-case\">mPK</jats:styled-content> exhibits a previously unobserved structural feature: the entrance of the intact S1 pocket is blocked by Glu217. In addition, molecular dynamics simulations and functional assays support the flexibility of Glu217 and suggest that this flexibility plays a role in regulating the activity of serine proteases.</jats:p></jats:sec><jats:sec><jats:title>Enzymes</jats:title><jats:p>EC: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" xlink:href=\"http://www.chem.qmul.ac.uk/iubmb/enzyme/EC3/4/21/34.html\">3.4.21.34</jats:ext-link></jats:p></jats:sec>","journal":"FEBS Letters","year":2018,"id":16575,"datarank":0.4267398222342636,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.11482359098228818,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.11482359098228818,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":5,"citers_with_citation_signal":4,"citers_with_endowment":4,"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":121847,"name":"Yayu Chen","orcid":null,"position":1,"is_corresponding":false},{"id":105975,"name":"Peng Xu","orcid":"0000-0002-7762-8934","position":2,"is_corresponding":false},{"id":112262,"name":"Peter A. Andreasen","orcid":null,"position":3,"is_corresponding":false},{"id":121848,"name":"Longguang Jiang","orcid":"0000-0002-4734-3778","position":4,"is_corresponding":false},{"id":114663,"name":"Jinyu Li","orcid":null,"position":5,"is_corresponding":false},{"id":121849,"name":"Mingdong Huang","orcid":"0000-0003-0085-9141","position":6,"is_corresponding":false},{"id":121846,"name":"Mingming Xu","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"30019481","pmcid":null,"openalex_id":"https://openalex.org/W2883654761","authors":[],"funders":[{"funder_name":"National Natural Science Foundation of China","grant_id":"21603033","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"31170707","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"31370737","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"31400637","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"31570745","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"31670739","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"U1405229","title":null},{"funder_name":"Natural Science Foundation of Fujian Province","grant_id":"2018J01729","title":null},{"funder_name":"Natural Science Foundation of Fujian Province","grant_id":"26181010","title":null}],"total_grants":9,"fwci":0.5771,"citation_percentile":0.69280081,"influential_citations":0,"citation_trend":[{"year":2019,"count":3},{"year":2021,"count":1},{"year":2022,"count":1},{"year":2023,"count":1},{"year":2024,"count":1}],"oa_status":"bronze","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://febs.onlinelibrary.wiley.com/doi/pdfdirect/10.1002/1873-3468.13191","host_type":"journal"},{"url":"https://febs.onlinelibrary.wiley.com/doi/pdfdirect/10.1002/1873-3468.13191","host_type":"BRONZE"},{"url":"https://febs.onlinelibrary.wiley.com/doi/pdfdirect/10.1002/1873-3468.13191","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2F1873-3468.13191","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/1873-3468.13191","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1002/1873-3468.13191","host_type":"publisher"},{"url":"https://febs.onlinelibrary.wiley.com/doi/pdf/10.1002/1873-3468.13191","host_type":"publisher"},{"url":"https://doi.org/10.1002/1873-3468.13191","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/30019481","host_type":"repository"},{"url":"https://pure.au.dk/portal/en/publications/50819f7f-977c-414b-8c64-2e28459daab1","host_type":""}],"fields_of_study":["Coagulation, Bradykinin, Polyphosphates, and Angioedema","Complement system in diseases","Protein Hydrolysis and Bioactive Peptides","Chemistry","Medicine","Biology","Amino Acid Sequence","Animals","Binding Sites","Catalysis","Catalytic Domain","Crystallography, X-Ray","Humans","Mice","Models, Molecular","Molecular Dynamics Simulation","Plasma Kallikrein","Protein Binding","Protein Conformation","Protein Interaction Domains and Motifs","Substrate Specificity"],"mesh_terms":["Amino Acid Sequence","Animals","Binding Sites","Catalysis","Humans","Models, Molecular","Protein Binding","Protein Conformation","Substrate Specificity","Crystallography, X-Ray","Catalytic Domain","Plasma Kallikrein","Mice","Protein Interaction Domains and Motifs","Molecular Dynamics Simulation"],"keywords":["Kallikrein","Flexibility (engineering)","Plasma","Chemistry","Crystal (programming language)","Crystallography","Biophysics","Physics","Biochemistry","Biology","Computer science","Mathematics","Statistics","Molecular dynamics","Flexibility","X-ray crystallography","Serine proteases","Plasma Kallikrein"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-02T11:45:38.981364Z","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":[]}