{"id":"https://openalex.org/W1998761138","doi":"https://doi.org/10.1107/s0907444905024340","title":"Mutation of surface residues to promote crystallization of activated factor XI as a complex with benzamidine: an essential step for the iterative structure-based design of factor XI inhibitors","display_name":"Mutation of surface residues to promote crystallization of activated factor XI as a complex with benzamidine: an essential step for the iterative structure-based design of factor XI inhibitors","publication_year":2005,"publication_date":"2005-09-28","ids":{"openalex":"https://openalex.org/W1998761138","doi":"https://doi.org/10.1107/s0907444905024340","mag":"1998761138","pmid":"https://pubmed.ncbi.nlm.nih.gov/16204896"},"language":"en","primary_location":{"id":"doi:10.1107/s0907444905024340","doi":"https://doi.org/10.1107/s0907444905024340","is_oa":false,"landing_page_url":"https://doi.org/10.1107/s0907444905024340","pdf_url":null,"source":{"id":"https://openalex.org/S114502960","display_name":"Acta Crystallographica Section D Biological Crystallography","issn_l":"0907-4449","issn":["0907-4449","1399-0047"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Acta Crystallographica Section D Biological Crystallography","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5100740373","display_name":"Lei Jin","orcid":"https://orcid.org/0000-0002-5602-1818","observed_orcids":["https://orcid.org/0000-0002-5602-1818"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Lei Jin","raw_affiliation_strings":["Daiichi Asubio Medical Research Laboratories LLC, USA. leijin05@yahoo.com"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Daiichi Asubio Medical Research Laboratories LLC, USA. leijin05@yahoo.com","institution_ids":[]}]},{"author_position":"middle","author":{"id":null,"display_name":"Pramod Pandey","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Pramod Pandey","raw_affiliation_strings":["Daiichi Asubio Medical Research Laboratories LLC, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Daiichi Asubio Medical Research Laboratories LLC, USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5073199142","display_name":"Robert E. Babine","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Robert E. Babine","raw_affiliation_strings":["Daiichi Asubio Medical Research Laboratories LLC, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Daiichi Asubio Medical Research Laboratories LLC, USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":null,"display_name":"David T. Weaver","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"David T. Weaver","raw_affiliation_strings":["Daiichi Asubio Medical Research Laboratories LLC, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Daiichi Asubio Medical Research Laboratories LLC, USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5109209369","display_name":"Sherin S. Abdel\u2010Meguid","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Sherin S. Abdel-Meguid","raw_affiliation_strings":["Daiichi Asubio Medical Research Laboratories LLC, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Daiichi Asubio Medical Research Laboratories LLC, USA","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5109146975","display_name":"James E. Strickler","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"James E. Strickler","raw_affiliation_strings":["Daiichi Asubio Medical Research Laboratories LLC, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Daiichi Asubio Medical Research Laboratories LLC, USA","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":4740,"currency":"USD","value_usd":4740},"apc_paid":null,"fwci":1.6681,"has_fulltext":false,"cited_by_count":30,"citation_normalized_percentile":{"value":0.81901639,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":97},"biblio":{"volume":"61","issue":"10","first_page":"1418","last_page":"1425"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11162","display_name":"Enzyme Structure and Function","score":0.8065999746322632,"subfield":{"id":"https://openalex.org/subfields/1315","display_name":"Structural Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11162","display_name":"Enzyme Structure and Function","score":0.8065999746322632,"subfield":{"id":"https://openalex.org/subfields/1315","display_name":"Structural Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11917","display_name":"Coagulation, Bradykinin, Polyphosphates, and Angioedema","score":0.0786999985575676,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11280","display_name":"Hemophilia Treatment and Research","score":0.060499999672174454,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/benzamidine","display_name":"benzamidine","score":0.9229999780654907},{"id":"https://openalex.org/keywords/crystal-structure","display_name":"crystal structure","score":0.4819999933242798},{"id":"https://openalex.org/keywords/small-molecule-inhibitors","display_name":"small molecule inhibitors","score":0.847000002861023},{"id":"https://openalex.org/keywords/structure-based-drug-design","display_name":"structure-based drug design","score":0.871999979019165},{"id":"https://openalex.org/keywords/ecotin","display_name":"ecotin","score":0.7099999785423279},{"id":"https://openalex.org/keywords/antithrombotic-agents","display_name":"antithrombotic agents","score":0.6949999928474426},{"id":"https://openalex.org/keywords/blood-coagulation","display_name":"coagulation","score":0.7680000066757202},{"id":"https://openalex.org/keywords/catalytic-domain","display_name":"catalytic domain","score":0.5669999718666077},{"id":"https://openalex.org/keywords/ligand-exchange","display_name":"ligand exchange","score":0.5559999942779541}],"concepts":[{"id":"https://openalex.org/C2779288520","wikidata":"https://www.wikidata.org/wiki/Q4890748","display_name":"Benzamidine","level":3,"score":0.9892377257347107},{"id":"https://openalex.org/C116569031","wikidata":"https://www.wikidata.org/wiki/Q899107","display_name":"Ligand (biochemistry)","level":3,"score":0.4543617367744446},{"id":"https://openalex.org/C203036418","wikidata":"https://www.wikidata.org/wiki/Q284256","display_name":"Crystallization","level":2,"score":0.4512672424316406},{"id":"https://openalex.org/C32909587","wikidata":"https://www.wikidata.org/wiki/Q11369","display_name":"Molecule","level":2,"score":0.451104998588562},{"id":"https://openalex.org/C115624301","wikidata":"https://www.wikidata.org/wiki/Q895901","display_name":"Crystal structure","level":2,"score":0.4228411316871643},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.42007771134376526},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.38352474570274353},{"id":"https://openalex.org/C8010536","wikidata":"https://www.wikidata.org/wiki/Q160398","display_name":"Crystallography","level":1,"score":0.37492257356643677},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.17742988467216492},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.13576194643974304},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.11102855205535889},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.10749167203903198}],"mesh":[{"descriptor_ui":"D001550","descriptor_name":"Benzamidines","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D001665","descriptor_name":"Binding Sites","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001779","descriptor_name":"Blood Coagulation Factors","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D002384","descriptor_name":"Catalysis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005172","descriptor_name":"Factor XI","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":true},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006860","descriptor_name":"Hydrogen Bonding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008024","descriptor_name":"Ligands","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008958","descriptor_name":"Models, Molecular","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009154","descriptor_name":"Mutation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D010455","descriptor_name":"Peptides","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D010843","descriptor_name":"Pichia","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D011485","descriptor_name":"Protein Binding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011487","descriptor_name":"Protein Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011994","descriptor_name":"Recombinant Proteins","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D012694","descriptor_name":"Serine","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D015945","descriptor_name":"Factor XIa","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D015945","descriptor_name":"Factor XIa","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D016296","descriptor_name":"Mutagenesis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016297","descriptor_name":"Mutagenesis, Site-Directed","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D018076","descriptor_name":"DNA, Complementary","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D018360","descriptor_name":"Crystallography, X-Ray","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D020128","descriptor_name":"Inhibitory Concentration 50","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D020134","descriptor_name":"Catalytic Domain","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D046911","descriptor_name":"Macromolecular Substances","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1107/s0907444905024340","doi":"https://doi.org/10.1107/s0907444905024340","is_oa":false,"landing_page_url":"https://doi.org/10.1107/s0907444905024340","pdf_url":null,"source":{"id":"https://openalex.org/S114502960","display_name":"Acta Crystallographica Section D Biological Crystallography","issn_l":"0907-4449","issn":["0907-4449","1399-0047"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Acta Crystallographica Section D Biological Crystallography","raw_type":"journal-article"},{"id":"pmid:16204896","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/16204896","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Acta crystallographica. Section D, Biological crystallography","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.428600013256073}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":17,"referenced_works":["https://openalex.org/W1489703191","https://openalex.org/W1539796472","https://openalex.org/W1548539963","https://openalex.org/W1599640293","https://openalex.org/W1757375456","https://openalex.org/W1828989025","https://openalex.org/W1967368955","https://openalex.org/W1985828707","https://openalex.org/W2004761712","https://openalex.org/W2025384625","https://openalex.org/W2039430475","https://openalex.org/W2069529679","https://openalex.org/W2072757169","https://openalex.org/W2079916746","https://openalex.org/W2089127095","https://openalex.org/W2091379422","https://openalex.org/W2976903704"],"related_works":["https://openalex.org/W2072757169","https://openalex.org/W2386319420","https://openalex.org/W2166319008","https://openalex.org/W2136144807","https://openalex.org/W1993804731","https://openalex.org/W2789859780","https://openalex.org/W2131424070","https://openalex.org/W7095102347","https://openalex.org/W2470327005","https://openalex.org/W2572688079"],"abstract_inverted_index":{"Activated":[0],"factor":[1],"XI":[2],"(FXIa)":[3],"is":[4,72],"a":[5,17,28,41,66,112],"key":[6],"enzyme":[7],"in":[8,54,96,139,146],"the":[9,13,38,44,48,97,106,140,147,162],"amplification":[10],"phase":[11],"of":[12,47,51,99,109,120,129,134,142,165],"blood-coagulation":[14],"cascade.":[15],"Thus,":[16],"selective":[18],"FXIa":[19,52,155,167],"inhibitor":[20],"may":[21],"have":[22,60,160],"lesser":[23],"bleeding":[24],"liabilities":[25],"and":[26,71],"provide":[27],"safe":[29],"alternative":[30],"for":[31,85],"antithrombosis":[32],"therapy":[33],"to":[34,74,104,125],"available":[35],"drugs":[36],"on":[37],"market.":[39],"In":[40,90,102],"previous":[42],"report,":[43],"crystal":[45,107,127],"structures":[46],"catalytic":[49],"domain":[50],"(rhFXI(370-607))":[53],"complex":[55],"with":[56,69,76,111,153],"various":[57],"ecotin":[58,64,79],"mutants":[59],"been":[61],"described.":[62],"However,":[63],"forms":[65],"matrix-like":[67],"interaction":[68],"rhFXI(370-607)":[70,92,110,135],"impossible":[73],"displace":[75],"small-molecule":[77,100,114,156,166],"inhibitors;":[78],"crystals":[80,149,159],"are":[81],"therefore":[82],"not":[83,94],"suitable":[84],"iterative":[86],"structure-based":[87,163],"ligand":[88],"design.":[89],"addition,":[91],"did":[93],"crystallize":[95],"presence":[98,141],"ligands.":[101],"order":[103],"obtain":[105],"structure":[108],"weak":[113],"ligand,":[115],"namely":[116],"benzamidine,":[117],"several":[118],"rounds":[119],"surface-residue":[121],"mutation":[122],"were":[123],"implemented":[124],"promote":[126],"formation":[128],"rhFXI(370-607).":[130],"A":[131],"quadruple":[132],"mutant":[133],"(rhFXI(370-607)-S434A,T475A,C482S,K437A)":[136],"readily":[137],"crystallized":[138],"benzamidine.":[143],"The":[144],"benzamidine":[145],"preformed":[148],"was":[150],"easily":[151],"exchanged":[152],"other":[154],"inhibitors.":[157,168],"These":[158],"facilitated":[161],"design":[164]},"counts_by_year":[{"year":2026,"cited_by_count":2},{"year":2022,"cited_by_count":1},{"year":2020,"cited_by_count":1},{"year":2019,"cited_by_count":1},{"year":2018,"cited_by_count":2},{"year":2016,"cited_by_count":3},{"year":2015,"cited_by_count":2},{"year":2013,"cited_by_count":3},{"year":2012,"cited_by_count":2}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2016-06-24T00:00:00"}