{"id":"https://openalex.org/W1964596038","doi":"https://doi.org/10.1021/ja201665x","title":"The Directive of the Protein: How Does Cytochrome P450 Select the Mechanism of Dopamine Formation?","display_name":"The Directive of the Protein: How Does Cytochrome P450 Select the Mechanism of Dopamine Formation?","publication_year":2011,"publication_date":"2011-05-03","ids":{"openalex":"https://openalex.org/W1964596038","doi":"https://doi.org/10.1021/ja201665x","mag":"1964596038","pmid":"https://pubmed.ncbi.nlm.nih.gov/21539368"},"language":"en","primary_location":{"id":"doi:10.1021/ja201665x","doi":"https://doi.org/10.1021/ja201665x","is_oa":false,"landing_page_url":"https://doi.org/10.1021/ja201665x","pdf_url":null,"source":{"id":"https://openalex.org/S111155417","display_name":"Journal of the American Chemical Society","issn_l":"0002-7863","issn":["0002-7863","1520-5126","1943-2984"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-a","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"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 the American Chemical Society","raw_type":"journal-article"},"parent_works":[],"lineage":["https://openalex.org/W1964596038"],"child_works_count":0,"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/A5054201075","display_name":"Patric Schyman","orcid":"https://orcid.org/0000-0002-5739-3891","observed_orcids":["https://orcid.org/0000-0002-5739-3891"]},"institutions":[{"id":"https://openalex.org/I197251160","display_name":"Hebrew University of Jerusalem","ror":"https://ror.org/03qxff017","country_code":"IL","type":"education","lineage":["https://openalex.org/I197251160"]}],"countries":["IL"],"is_corresponding":false,"raw_author_name":"Patric Schyman","raw_affiliation_strings":["Institute of Chemistry and The Lise Meitner-Minerva Center for Computational Quantum Chemistry, The Hebrew University of Jerusalem, 91904, Jerusalem, Israel"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Institute of Chemistry and The Lise Meitner-Minerva Center for Computational Quantum Chemistry, The Hebrew University of Jerusalem, 91904, Jerusalem, Israel","institution_ids":["https://openalex.org/I197251160"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5084218246","display_name":"Wenzhen Lai","orcid":"https://orcid.org/0000-0003-2830-6151","observed_orcids":["https://orcid.org/0000-0003-2830-6151"]},"institutions":[{"id":"https://openalex.org/I197251160","display_name":"Hebrew University of Jerusalem","ror":"https://ror.org/03qxff017","country_code":"IL","type":"education","lineage":["https://openalex.org/I197251160"]}],"countries":["IL"],"is_corresponding":false,"raw_author_name":"Wenzhen Lai","raw_affiliation_strings":["Institute of Chemistry and The Lise Meitner-Minerva Center for Computational Quantum Chemistry, The Hebrew University of Jerusalem, 91904, Jerusalem, Israel"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Institute of Chemistry and The Lise Meitner-Minerva Center for Computational Quantum Chemistry, The Hebrew University of Jerusalem, 91904, Jerusalem, Israel","institution_ids":["https://openalex.org/I197251160"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100334211","display_name":"Hui Chen","orcid":"https://orcid.org/0000-0003-0483-8786","observed_orcids":["https://orcid.org/0000-0003-0483-8786"]},"institutions":[{"id":"https://openalex.org/I197251160","display_name":"Hebrew University of Jerusalem","ror":"https://ror.org/03qxff017","country_code":"IL","type":"education","lineage":["https://openalex.org/I197251160"]}],"countries":["IL"],"is_corresponding":false,"raw_author_name":"Hui Chen","raw_affiliation_strings":["Institute of Chemistry and The Lise Meitner-Minerva Center for Computational Quantum Chemistry, The Hebrew University of Jerusalem, 91904, Jerusalem, Israel"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Institute of Chemistry and The Lise Meitner-Minerva Center for Computational Quantum Chemistry, The Hebrew University of Jerusalem, 91904, Jerusalem, Israel","institution_ids":["https://openalex.org/I197251160"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5001158309","display_name":"Yong Wang","orcid":"https://orcid.org/0000-0002-7668-2234","observed_orcids":["https://orcid.org/0000-0002-7668-2234"]},"institutions":[{"id":"https://openalex.org/I197251160","display_name":"Hebrew University of Jerusalem","ror":"https://ror.org/03qxff017","country_code":"IL","type":"education","lineage":["https://openalex.org/I197251160"]}],"countries":["IL"],"is_corresponding":false,"raw_author_name":"Yong Wang","raw_affiliation_strings":["Institute of Chemistry and The Lise Meitner-Minerva Center for Computational Quantum Chemistry, The Hebrew University of Jerusalem, 91904, Jerusalem, Israel"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Institute of Chemistry and The Lise Meitner-Minerva Center for Computational Quantum Chemistry, The Hebrew University of Jerusalem, 91904, Jerusalem, Israel","institution_ids":["https://openalex.org/I197251160"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5026786226","display_name":"Sason S. Shaik","orcid":"https://orcid.org/0000-0001-7643-9421","observed_orcids":["https://orcid.org/0000-0001-7643-9421"]},"institutions":[{"id":"https://openalex.org/I197251160","display_name":"Hebrew University of Jerusalem","ror":"https://ror.org/03qxff017","country_code":"IL","type":"education","lineage":["https://openalex.org/I197251160"]}],"countries":["IL"],"is_corresponding":true,"raw_author_name":"Sason Shaik","raw_affiliation_strings":["Institute of Chemistry and The Lise Meitner-Minerva Center for Computational Quantum Chemistry, The Hebrew University of Jerusalem, 91904, Jerusalem, Israel"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Institute of Chemistry and The Lise Meitner-Minerva Center for Computational Quantum Chemistry, The Hebrew University of Jerusalem, 91904, Jerusalem, Israel","institution_ids":["https://openalex.org/I197251160"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5026786226"],"corresponding_institution_ids":["https://openalex.org/I197251160"],"apc_list":{"value":4500,"currency":"USD","value_usd":4500},"apc_paid":null,"fwci":14.0073,"has_fulltext":false,"cited_by_count":234,"citation_normalized_percentile":{"value":0.99394037,"is_in_top_1_percent":true,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":96,"max":100},"biblio":{"volume":"133","issue":"20","first_page":"7977","last_page":"7984"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11747","display_name":"Metal-Catalyzed Oxygenation Mechanisms","score":0.9951000213623047,"subfield":{"id":"https://openalex.org/subfields/1604","display_name":"Inorganic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},"topics":[{"id":"https://openalex.org/T11747","display_name":"Metal-Catalyzed Oxygenation Mechanisms","score":0.9951000213623047,"subfield":{"id":"https://openalex.org/subfields/1604","display_name":"Inorganic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T12191","display_name":"Physical Organic Chemistry and Reaction Kinetics","score":0.0034000000450760126,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10375","display_name":"Pharmacogenetics and Drug Metabolism","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/dopamine-synthesis","display_name":"dopamine synthesis","score":0.7770000100135803},{"id":"https://openalex.org/keywords/cyp2d6","display_name":"CYP2D6","score":0.8479999899864197},{"id":"https://openalex.org/keywords/reaction-mechanism","display_name":"reaction mechanism","score":0.5270000100135803},{"id":"https://openalex.org/keywords/meisenheimer-complexes","display_name":"Meisenheimer complexes","score":0.7419999837875366},{"id":"https://openalex.org/keywords/compound-i","display_name":"compound I","score":0.8939999938011169},{"id":"https://openalex.org/keywords/hydrogen-atom-transfer","display_name":"hydrogen atom transfer","score":0.6589999794960022},{"id":"https://openalex.org/keywords/external-electric-field","display_name":"external electric field","score":0.6190000176429749},{"id":"https://openalex.org/keywords/qm-mm","display_name":"QM/MM","score":0.6909999847412109}],"concepts":[{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.9611132740974426},{"id":"https://openalex.org/C2781109383","wikidata":"https://www.wikidata.org/wiki/Q898497","display_name":"Hydroxylation","level":3,"score":0.5409733653068542},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.47074422240257263},{"id":"https://openalex.org/C513476851","wikidata":"https://www.wikidata.org/wiki/Q170304","display_name":"Dopamine","level":2,"score":0.46305298805236816},{"id":"https://openalex.org/C75473681","wikidata":"https://www.wikidata.org/wiki/Q188651","display_name":"Photochemistry","level":1,"score":0.4552052319049835},{"id":"https://openalex.org/C45119746","wikidata":"https://www.wikidata.org/wiki/Q205949","display_name":"Exothermic reaction","level":2,"score":0.445403516292572},{"id":"https://openalex.org/C2776077682","wikidata":"https://www.wikidata.org/wiki/Q165930","display_name":"Tyramine","level":2,"score":0.44525933265686035},{"id":"https://openalex.org/C147597530","wikidata":"https://www.wikidata.org/wiki/Q369472","display_name":"Computational chemistry","level":1,"score":0.33613523840904236},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.2211644947528839},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.19167792797088623},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.09604814648628235},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.0},{"id":"https://openalex.org/C169760540","wikidata":"https://www.wikidata.org/wiki/Q207011","display_name":"Neuroscience","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D003577","descriptor_name":"Cytochrome P-450 Enzyme System","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D004298","descriptor_name":"Dopamine","qualifier_ui":"Q000096","qualifier_name":"biosynthesis","is_major_topic":true},{"descriptor_ui":"D008958","descriptor_name":"Models, Molecular","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D010084","descriptor_name":"Oxidation-Reduction","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011506","descriptor_name":"Proteins","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D011789","descriptor_name":"Quantum Theory","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1021/ja201665x","doi":"https://doi.org/10.1021/ja201665x","is_oa":false,"landing_page_url":"https://doi.org/10.1021/ja201665x","pdf_url":null,"source":{"id":"https://openalex.org/S111155417","display_name":"Journal of the American Chemical Society","issn_l":"0002-7863","issn":["0002-7863","1520-5126","1943-2984"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-a","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"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 the American Chemical Society","raw_type":"journal-article"},{"id":"pmid:21539368","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/21539368","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":"Journal of the American Chemical Society","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":69,"referenced_works":["https://openalex.org/W139881401","https://openalex.org/W1564105979","https://openalex.org/W1923129209","https://openalex.org/W1964720506","https://openalex.org/W1966182479","https://openalex.org/W1968400590","https://openalex.org/W1972127956","https://openalex.org/W1975262546","https://openalex.org/W1976793490","https://openalex.org/W1976972723","https://openalex.org/W1978615429","https://openalex.org/W1984465513","https://openalex.org/W1988485815","https://openalex.org/W1998528771","https://openalex.org/W1998710563","https://openalex.org/W1999458467","https://openalex.org/W1999664769","https://openalex.org/W2002583489","https://openalex.org/W2008825099","https://openalex.org/W2010724535","https://openalex.org/W2015642465","https://openalex.org/W2021713602","https://openalex.org/W2023271753","https://openalex.org/W2024872256","https://openalex.org/W2025161609","https://openalex.org/W2026423508","https://openalex.org/W2027408247","https://openalex.org/W2028022118","https://openalex.org/W2029326212","https://openalex.org/W2033035711","https://openalex.org/W2038028459","https://openalex.org/W2041315283","https://openalex.org/W2042706608","https://openalex.org/W2045836463","https://openalex.org/W2049557754","https://openalex.org/W2052559859","https://openalex.org/W2053793146","https://openalex.org/W2054605198","https://openalex.org/W2055104777","https://openalex.org/W2058210956","https://openalex.org/W2060453024","https://openalex.org/W2060943223","https://openalex.org/W2065698723","https://openalex.org/W2065895273","https://openalex.org/W2073390459","https://openalex.org/W2073860917","https://openalex.org/W2077621515","https://openalex.org/W2080961736","https://openalex.org/W2086957099","https://openalex.org/W2092157292","https://openalex.org/W2094941054","https://openalex.org/W2095538261","https://openalex.org/W2100032379","https://openalex.org/W2105587896","https://openalex.org/W2132273889","https://openalex.org/W2142419145","https://openalex.org/W2143981217","https://openalex.org/W2144860443","https://openalex.org/W2146341684","https://openalex.org/W2146702232","https://openalex.org/W2150641509","https://openalex.org/W2152997175","https://openalex.org/W2154393674","https://openalex.org/W2157091272","https://openalex.org/W2159529011","https://openalex.org/W2160316343","https://openalex.org/W2162166182","https://openalex.org/W2527870633","https://openalex.org/W4235876314"],"related_works":["https://openalex.org/W1593208144","https://openalex.org/W2281443107","https://openalex.org/W2154395552","https://openalex.org/W1991127167","https://openalex.org/W4406036394","https://openalex.org/W2047541051","https://openalex.org/W1989479233","https://openalex.org/W2531647377","https://openalex.org/W2003535968","https://openalex.org/W3203596310"],"abstract_inverted_index":{"Dopamine":[0],"can":[1,168],"be":[2],"generated":[3],"from":[4,52],"tyramine":[5,59],"via":[6],"arene":[7],"hydroxylation":[8],"catalyzed":[9],"by":[10,70,80,97],"a":[11,44,71,108,117,137,156],"cytochrome":[12],"P450":[13],"enzyme":[14],"(CYP2D6).":[15],"Our":[16],"quantum":[17],"mechanical/molecular":[18],"mechanical":[19],"(QM/MM)":[20],"results":[21],"reveal":[22],"the":[23,27,31,37,41,53,58,61,64,89,93,103,113,127,132,141,144,150,173],"decisive":[24],"impact":[25],"of":[26,36,57,63,131,143,152],"protein":[28,133],"in":[29,88],"selecting":[30],"'best'":[32],"reaction":[33,115],"mechanism.":[34],"Instead":[35],"traditional":[38],"Meisenheimer-complex":[39],"mechanism,":[40],"study":[42],"reveals":[43],"mechanism":[45,84],"involving":[46],"an":[47],"initial":[48],"hydrogen":[49],"atom":[50],"transfer":[51],"phenolic":[54],"hydroxyl":[55],"group":[56],"to":[60,78],"iron-oxo":[62],"compound":[65],"I":[66,99],"(Cpd":[67],"I),":[68],"followed":[69],"ring-\u03c0":[72],"radical":[73],"rebound":[74],"that":[75,126,139,164],"eventually":[76],"leads":[77],"dopamine":[79,153],"keto-enol":[81],"rearrangement.":[82],"This":[83],"is":[85,100,121,124,162],"not":[86,106],"viable":[87],"gas":[90],"phase":[91],"since":[92],"O-H":[94],"bond":[95],"activation":[96],"Cpd":[98],"endothermic":[101],"and":[102,120,147],"process":[104,174],"does":[105],"form":[107],"stable":[109],"intermediate.":[110],"By":[111],"contrast,":[112],"in-protein":[114],"has":[116],"low":[118],"barrier":[119],"exothermic.":[122],"It":[123],"shown":[125,163],"local":[128],"electric":[129,166],"field":[130],"environment":[134],"serves":[135],"as":[136],"template":[138],"stabilizes":[140],"intermediate":[142],"H-abstraction":[145],"step":[146],"thereby":[148],"mediates":[149],"catalysis":[151],"formation":[154],"at":[155],"lower":[157],"energy":[158],"cost.":[159],"Furthermore,":[160],"it":[161],"external":[165],"fields":[167],"either":[169],"catalyze":[170],"or":[171],"inhibit":[172],"depending":[175],"on":[176],"their":[177],"directionality.":[178]},"counts_by_year":[{"year":2026,"cited_by_count":3},{"year":2025,"cited_by_count":8},{"year":2024,"cited_by_count":5},{"year":2023,"cited_by_count":7},{"year":2022,"cited_by_count":11},{"year":2021,"cited_by_count":12},{"year":2020,"cited_by_count":13},{"year":2019,"cited_by_count":17},{"year":2018,"cited_by_count":12},{"year":2017,"cited_by_count":15},{"year":2016,"cited_by_count":21},{"year":2015,"cited_by_count":24},{"year":2014,"cited_by_count":27},{"year":2013,"cited_by_count":31},{"year":2012,"cited_by_count":26}],"updated_date":"2026-11-14T11:04:58.165337","created_date":"2016-06-24T00:00:00"}