{"id":"https://openalex.org/W4384028690","doi":"https://doi.org/10.1021/acs.jcim.3c00331","title":"Structural and Computational Analyses of the Unique Interactions of Opicapone in the Binding Pocket of Catechol <i>O</i>-Methyltransferase: A Crystallographic Study and Fragment Molecular Orbital Analyses","display_name":"Structural and Computational Analyses of the Unique Interactions of Opicapone in the Binding Pocket of Catechol <i>O</i>-Methyltransferase: A Crystallographic Study and Fragment Molecular Orbital Analyses","publication_year":2023,"publication_date":"2023-07-12","ids":{"openalex":"https://openalex.org/W4384028690","doi":"https://doi.org/10.1021/acs.jcim.3c00331","pmid":"https://pubmed.ncbi.nlm.nih.gov/37436881"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.3c00331","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.3c00331","pdf_url":null,"source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},"type":"article","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/A5020031597","display_name":"Katsuki Takebe","orcid":"https://orcid.org/0000-0002-1611-1042"},"institutions":[{"id":"https://openalex.org/I98285908","display_name":"Osaka University","ror":"https://ror.org/035t8zc32","country_code":"JP","type":"education","lineage":["https://openalex.org/I98285908"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Katsuki Takebe","raw_affiliation_strings":["Oral and Maxillofacial Surgery II, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871, Japan"],"affiliations":[{"raw_affiliation_string":"Oral and Maxillofacial Surgery II, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871, Japan","institution_ids":["https://openalex.org/I98285908"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5065673016","display_name":"Mamoru Suzuki","orcid":"https://orcid.org/0000-0001-7071-5093"},"institutions":[{"id":"https://openalex.org/I98285908","display_name":"Osaka University","ror":"https://ror.org/035t8zc32","country_code":"JP","type":"education","lineage":["https://openalex.org/I98285908"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Mamoru Suzuki","raw_affiliation_strings":["Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan"],"affiliations":[{"raw_affiliation_string":"Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan","institution_ids":["https://openalex.org/I98285908"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5009694824","display_name":"Takao Kuwada-Kusunose","orcid":null},"institutions":[{"id":"https://openalex.org/I104946051","display_name":"Nihon University","ror":"https://ror.org/05jk51a88","country_code":"JP","type":"education","lineage":["https://openalex.org/I104946051"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Takao Kuwada-Kusunose","raw_affiliation_strings":["School of Dentistry at Matsudo, Nihon University, 2-870-1 Sakaecho-nishi, Matsudo, Chiba 271-8587, Japan"],"affiliations":[{"raw_affiliation_string":"School of Dentistry at Matsudo, Nihon University, 2-870-1 Sakaecho-nishi, Matsudo, Chiba 271-8587, Japan","institution_ids":["https://openalex.org/I104946051"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5104353238","display_name":"Satoko Shirai","orcid":null},"institutions":[{"id":"https://openalex.org/I36296616","display_name":"Hoshi University","ror":"https://ror.org/01mrvbd33","country_code":"JP","type":"education","lineage":["https://openalex.org/I36296616"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Satoko Shirai","raw_affiliation_strings":["School of Pharmacy and Pharmaceutical Sciences, Hoshi University, Shinagawa, Tokyo 142-8501, Japan"],"affiliations":[{"raw_affiliation_string":"School of Pharmacy and Pharmaceutical Sciences, Hoshi University, Shinagawa, Tokyo 142-8501, Japan","institution_ids":["https://openalex.org/I36296616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5079773397","display_name":"Kaori Fukuzawa","orcid":"https://orcid.org/0000-0001-5357-8250"},"institutions":[{"id":"https://openalex.org/I36296616","display_name":"Hoshi University","ror":"https://ror.org/01mrvbd33","country_code":"JP","type":"education","lineage":["https://openalex.org/I36296616"]},{"id":"https://openalex.org/I98285908","display_name":"Osaka University","ror":"https://ror.org/035t8zc32","country_code":"JP","type":"education","lineage":["https://openalex.org/I98285908"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Kaori Fukuzawa","raw_affiliation_strings":["Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan","School of Pharmacy and Pharmaceutical Sciences, Hoshi University, Shinagawa, Tokyo 142-8501, Japan"],"affiliations":[{"raw_affiliation_string":"Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan","institution_ids":["https://openalex.org/I98285908"]},{"raw_affiliation_string":"School of Pharmacy and Pharmaceutical Sciences, Hoshi University, Shinagawa, Tokyo 142-8501, Japan","institution_ids":["https://openalex.org/I36296616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5000867580","display_name":"Tomoko Takamiya","orcid":"https://orcid.org/0000-0003-0821-9675"},"institutions":[{"id":"https://openalex.org/I104946051","display_name":"Nihon University","ror":"https://ror.org/05jk51a88","country_code":"JP","type":"education","lineage":["https://openalex.org/I104946051"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Tomoko Takamiya","raw_affiliation_strings":["School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan"],"affiliations":[{"raw_affiliation_string":"School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan","institution_ids":["https://openalex.org/I104946051"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5061542199","display_name":"Narikazu Uzawa","orcid":"https://orcid.org/0000-0001-5390-6875"},"institutions":[{"id":"https://openalex.org/I98285908","display_name":"Osaka University","ror":"https://ror.org/035t8zc32","country_code":"JP","type":"education","lineage":["https://openalex.org/I98285908"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Narikazu Uzawa","raw_affiliation_strings":["Oral and Maxillofacial Surgery II, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871, Japan"],"affiliations":[{"raw_affiliation_string":"Oral and Maxillofacial Surgery II, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871, Japan","institution_ids":["https://openalex.org/I98285908"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5087605806","display_name":"Hiroshi Iijima","orcid":"https://orcid.org/0000-0001-8402-0292"},"institutions":[{"id":"https://openalex.org/I104946051","display_name":"Nihon University","ror":"https://ror.org/05jk51a88","country_code":"JP","type":"education","lineage":["https://openalex.org/I104946051"]}],"countries":["JP"],"is_corresponding":true,"raw_author_name":"Hiroshi Iijima","raw_affiliation_strings":["CBI Research Institute, 3-11-1 Shibaura, Minato-ku, Tokyo 108-0023, Japan","School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan"],"affiliations":[{"raw_affiliation_string":"CBI Research Institute, 3-11-1 Shibaura, Minato-ku, Tokyo 108-0023, Japan","institution_ids":[]},{"raw_affiliation_string":"School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan","institution_ids":["https://openalex.org/I104946051"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":8,"corresponding_author_ids":["https://openalex.org/A5087605806"],"corresponding_institution_ids":["https://openalex.org/I104946051"],"apc_list":null,"apc_paid":null,"fwci":0.7973,"has_fulltext":false,"cited_by_count":5,"citation_normalized_percentile":{"value":0.73203664,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":97,"max":98},"biblio":{"volume":"63","issue":"14","first_page":"4468","last_page":"4476"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10493","display_name":"Ion channel regulation and function","score":0.9800000190734863,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular 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/T10493","display_name":"Ion channel regulation and function","score":0.9800000190734863,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular 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/T10217","display_name":"Cardiac electrophysiology and arrhythmias","score":0.970300018787384,"subfield":{"id":"https://openalex.org/subfields/2705","display_name":"Cardiology and Cardiovascular Medicine"},"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/T13047","display_name":"Pharmacological Receptor Mechanisms and Effects","score":0.9695000052452087,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular 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"}}],"keywords":[{"id":"https://openalex.org/keywords/catechol-o-methyl-transferase","display_name":"Catechol-O-methyl transferase","score":0.8678682446479797},{"id":"https://openalex.org/keywords/moiety","display_name":"Moiety","score":0.77613365650177},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.7537498474121094},{"id":"https://openalex.org/keywords/catechol","display_name":"Catechol","score":0.7271275520324707},{"id":"https://openalex.org/keywords/stereochemistry","display_name":"Stereochemistry","score":0.6190006136894226},{"id":"https://openalex.org/keywords/molecular-orbital","display_name":"Molecular orbital","score":0.5456526875495911},{"id":"https://openalex.org/keywords/methyltransferase","display_name":"Methyltransferase","score":0.508691132068634},{"id":"https://openalex.org/keywords/active-site","display_name":"Active site","score":0.47980716824531555},{"id":"https://openalex.org/keywords/transferase","display_name":"Transferase","score":0.4691936671733856},{"id":"https://openalex.org/keywords/enzyme","display_name":"Enzyme","score":0.4643353223800659},{"id":"https://openalex.org/keywords/entacapone","display_name":"Entacapone","score":0.432143896818161},{"id":"https://openalex.org/keywords/molecule","display_name":"Molecule","score":0.4275762140750885},{"id":"https://openalex.org/keywords/ring","display_name":"Ring (chemistry)","score":0.4214288294315338},{"id":"https://openalex.org/keywords/dna","display_name":"DNA","score":0.28301870822906494},{"id":"https://openalex.org/keywords/biochemistry","display_name":"Biochemistry","score":0.18678057193756104},{"id":"https://openalex.org/keywords/methylation","display_name":"Methylation","score":0.09125727415084839},{"id":"https://openalex.org/keywords/organic-chemistry","display_name":"Organic chemistry","score":0.08702236413955688},{"id":"https://openalex.org/keywords/levodopa","display_name":"Levodopa","score":0.07370129227638245}],"concepts":[{"id":"https://openalex.org/C185361966","wikidata":"https://www.wikidata.org/wiki/Q94291140","display_name":"Catechol-O-methyl transferase","level":4,"score":0.8678682446479797},{"id":"https://openalex.org/C2776568683","wikidata":"https://www.wikidata.org/wiki/Q23005640","display_name":"Moiety","level":2,"score":0.77613365650177},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.7537498474121094},{"id":"https://openalex.org/C2777713698","wikidata":"https://www.wikidata.org/wiki/Q282440","display_name":"Catechol","level":2,"score":0.7271275520324707},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.6190006136894226},{"id":"https://openalex.org/C139358910","wikidata":"https://www.wikidata.org/wiki/Q725417","display_name":"Molecular orbital","level":3,"score":0.5456526875495911},{"id":"https://openalex.org/C91965660","wikidata":"https://www.wikidata.org/wiki/Q415875","display_name":"Methyltransferase","level":4,"score":0.508691132068634},{"id":"https://openalex.org/C41183919","wikidata":"https://www.wikidata.org/wiki/Q423026","display_name":"Active site","level":3,"score":0.47980716824531555},{"id":"https://openalex.org/C2776376580","wikidata":"https://www.wikidata.org/wiki/Q407355","display_name":"Transferase","level":3,"score":0.4691936671733856},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.4643353223800659},{"id":"https://openalex.org/C2776976799","wikidata":"https://www.wikidata.org/wiki/Q416444","display_name":"Entacapone","level":5,"score":0.432143896818161},{"id":"https://openalex.org/C32909587","wikidata":"https://www.wikidata.org/wiki/Q11369","display_name":"Molecule","level":2,"score":0.4275762140750885},{"id":"https://openalex.org/C2780378348","wikidata":"https://www.wikidata.org/wiki/Q25351438","display_name":"Ring (chemistry)","level":2,"score":0.4214288294315338},{"id":"https://openalex.org/C552990157","wikidata":"https://www.wikidata.org/wiki/Q7430","display_name":"DNA","level":2,"score":0.28301870822906494},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.18678057193756104},{"id":"https://openalex.org/C33288867","wikidata":"https://www.wikidata.org/wiki/Q518328","display_name":"Methylation","level":3,"score":0.09125727415084839},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.08702236413955688},{"id":"https://openalex.org/C2780304432","wikidata":"https://www.wikidata.org/wiki/Q300989","display_name":"Levodopa","level":4,"score":0.07370129227638245},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0},{"id":"https://openalex.org/C142724271","wikidata":"https://www.wikidata.org/wiki/Q7208","display_name":"Pathology","level":1,"score":0.0},{"id":"https://openalex.org/C2779734285","wikidata":"https://www.wikidata.org/wiki/Q11085","display_name":"Parkinson's disease","level":3,"score":0.0},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.0},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.0},{"id":"https://openalex.org/C180754005","wikidata":"https://www.wikidata.org/wiki/Q80726","display_name":"Allele","level":3,"score":0.0}],"mesh":[{"descriptor_ui":"D000077867","descriptor_name":"Tolcapone","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000077867","descriptor_name":"Tolcapone","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000077867","descriptor_name":"Tolcapone","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002394","descriptor_name":"Catechol O-Methyltransferase","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D002394","descriptor_name":"Catechol O-Methyltransferase","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D002394","descriptor_name":"Catechol O-Methyltransferase","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D002396","descriptor_name":"Catechols","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009574","descriptor_name":"Nitro Compounds","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D010069","descriptor_name":"Oxadiazoles","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D010069","descriptor_name":"Oxadiazoles","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D010069","descriptor_name":"Oxadiazoles","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D065098","descriptor_name":"Catechol O-Methyltransferase Inhibitors","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D065098","descriptor_name":"Catechol O-Methyltransferase Inhibitors","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D065098","descriptor_name":"Catechol O-Methyltransferase Inhibitors","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D065098","descriptor_name":"Catechol O-Methyltransferase Inhibitors","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D065098","descriptor_name":"Catechol O-Methyltransferase Inhibitors","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D065098","descriptor_name":"Catechol O-Methyltransferase Inhibitors","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true}],"locations_count":2,"locations":[{"id":"doi:10.1021/acs.jcim.3c00331","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.3c00331","pdf_url":null,"source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},{"id":"pmid:37436881","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/37436881","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,"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":"Journal of chemical information and modeling","raw_type":null}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/12","score":0.5199999809265137,"display_name":"Responsible consumption and production"}],"awards":[{"id":"https://openalex.org/G182507809","display_name":null,"funder_award_id":"P18am0101070 0318","funder_id":"https://openalex.org/F4320311405","funder_display_name":"Japan Agency for Medical Research and Development"},{"id":"https://openalex.org/G3802449110","display_name":null,"funder_award_id":"P18am0101070 2556","funder_id":"https://openalex.org/F4320311405","funder_display_name":"Japan Agency for Medical Research and Development"},{"id":"https://openalex.org/G5545922637","display_name":null,"funder_award_id":"JP15K08034","funder_id":"https://openalex.org/F4320334764","funder_display_name":"Japan Society for the Promotion of Science"},{"id":"https://openalex.org/G6047590619","display_name":null,"funder_award_id":"JP21am0101113","funder_id":"https://openalex.org/F4320311405","funder_display_name":"Japan Agency for Medical Research and Development"},{"id":"https://openalex.org/G6741547606","display_name":null,"funder_award_id":"CR-21-02","funder_id":"https://openalex.org/F4320336670","funder_display_name":"Institute for Protein Research, Osaka University"}],"funders":[{"id":"https://openalex.org/F4320311405","display_name":"Japan Agency for Medical Research and Development","ror":"https://ror.org/004rtk039"},{"id":"https://openalex.org/F4320312698","display_name":"Tokyo Biochemical Research Foundation","ror":"https://ror.org/04bxrzx68"},{"id":"https://openalex.org/F4320334764","display_name":"Japan Society for the Promotion of Science","ror":"https://ror.org/00hhkn466"},{"id":"https://openalex.org/F4320336670","display_name":"Institute for Protein Research, Osaka University","ror":null}],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":36,"referenced_works":["https://openalex.org/W1497529955","https://openalex.org/W1518956512","https://openalex.org/W1955911053","https://openalex.org/W1965770627","https://openalex.org/W1967566074","https://openalex.org/W1980384054","https://openalex.org/W1984593979","https://openalex.org/W1989842308","https://openalex.org/W2008288225","https://openalex.org/W2016759354","https://openalex.org/W2019322974","https://openalex.org/W2033881399","https://openalex.org/W2034691697","https://openalex.org/W2095227025","https://openalex.org/W2096712882","https://openalex.org/W2110808180","https://openalex.org/W2118233996","https://openalex.org/W2118622794","https://openalex.org/W2124026197","https://openalex.org/W2131197116","https://openalex.org/W2131260498","https://openalex.org/W2146080841","https://openalex.org/W2159211495","https://openalex.org/W2180229411","https://openalex.org/W2195010995","https://openalex.org/W2513815885","https://openalex.org/W2526408712","https://openalex.org/W2730550714","https://openalex.org/W2778728953","https://openalex.org/W2892998861","https://openalex.org/W2935898954","https://openalex.org/W3021815617","https://openalex.org/W3113502995","https://openalex.org/W3122608869","https://openalex.org/W4248872320","https://openalex.org/W4251872734"],"related_works":["https://openalex.org/W3026235369","https://openalex.org/W2118896395","https://openalex.org/W2000003394","https://openalex.org/W9620540","https://openalex.org/W1991080312","https://openalex.org/W1984156254","https://openalex.org/W1984702297","https://openalex.org/W2042308210","https://openalex.org/W2095754699","https://openalex.org/W1980971295"],"abstract_inverted_index":{"A":[0],"third-generation":[1],"inhibitor":[2,159,241],"of":[3,52,58,66,75,95,108,131,137,142,176,193,213],"catechol":[4,120],"<i>O</i>-methyltransferase":[5],"(COMT),":[6],"opicapone":[7],"(<b>1</b>),":[8],"has":[9,160],"the":[10,15,46,56,59,64,67,72,89,93,102,105,119,128,143,154,173,181,185,191,207,211,214],"3-nitrocatechol":[11,60],"scaffold":[12],"as":[13,19,196,235,243],"do":[14],"second-generation":[16],"inhibitors":[17],"such":[18],"entacapone":[20],"(<b>2</b>)":[21],"and":[22,78,98,104,112,146,170,225,242],"tolcapone":[23],"(<b>3</b>),":[24],"but":[25],"only":[26],"<b>1</b>":[27,53,109,219,230],"can":[28],"sustainably":[29],"inhibit":[30,232],"COMT":[31,169,226,233],"activity":[32],"making":[33],"it":[34],"suitable":[35],"for":[36],"a":[37,124,150,166,197,203,221,236,244],"once-daily":[38],"regimen.":[39],"These":[40],"improvements":[41],"should":[42],"be":[43],"attributed":[44],"to":[45,164,200,210],"optimized":[47],"sidechain":[48,68,129],"moiety":[49,69],"(oxidopyridyloxadiazolyl":[50],"group)":[51],"substituted":[54],"at":[55],"5-position":[57],"ring.":[61],"We":[62],"analyzed":[63],"role":[65,192],"by":[70,149],"solving":[71],"crystal":[73],"structures":[74],"COMT/<i>S</i>-adenosylmethionine":[76],"(SAM)/Mg/<b>1</b>":[77],"COMT/<i>S</i>-adenosylhomocysteine":[79],"(SAH)/Mg/<b>1</b>":[80],"complexes.":[81,116],"Fragment":[82],"molecular":[83],"orbital":[84],"(FMO)":[85],"calculations":[86],"elucidated":[87],"that":[88,189,218,229],"dispersion":[90],"interaction":[91],"between":[92],"sidechains":[94],"Leu":[96],"198":[97],"Met":[99],"201":[100],"on":[101],"\u03b26\u03b27-loop":[103],"oxidopyridine":[106],"ring":[107],"were":[110],"unique":[111],"important":[113],"in":[114,127,153,180],"both":[115],"In":[117],"contrast,":[118],"binding":[121],"site":[122,209],"made":[123],"remarkable":[125],"difference":[126],"conformation":[130],"Lys":[132,138,177,194],"144.":[133],"The":[134,216],"\u03b5-amino":[135],"group":[136],"144":[139,178,195],"was":[140,147],"outside":[141,212],"catalytic":[144,198],"pocket":[145],"replaced":[148],"water":[151],"molecule":[152],"COMT/SAH/Mg/<b>1</b>":[155,182],"complex.":[156],"No":[157],"nitrocatechol":[158],"ever":[161],"been":[162],"reported":[163],"make":[165],"complex":[167,183,222],"with":[168,223],"SAH.":[171],"Thus,":[172],"conformational":[174],"change":[175],"found":[179],"is":[184],"first":[186],"crystallographic":[187],"evidence":[188],"supports":[190],"base":[199],"take":[201],"out":[202],"proton":[204],"ion":[205],"from":[206],"reaction":[208],"enzyme.":[215],"fact":[217],"generated":[220],"SAH":[224],"also":[227],"suggests":[228],"could":[231],"twofold,":[234],"typical":[237],"substrate":[238],"mimic":[239],"competitive":[240],"product-inhibition":[245],"enhancer.":[246]},"counts_by_year":[{"year":2024,"cited_by_count":5}],"updated_date":"2025-11-06T03:46:38.306776","created_date":"2025-10-10T00:00:00"}