{"id":"https://openalex.org/W2604162743","doi":"https://doi.org/10.1021/acs.jcim.6b00759","title":"Mechanism of Cytochrome P450 17A1-Catalyzed Hydroxylase and Lyase Reactions","display_name":"Mechanism of Cytochrome P450 17A1-Catalyzed Hydroxylase and Lyase Reactions","publication_year":2017,"publication_date":"2017-04-07","ids":{"openalex":"https://openalex.org/W2604162743","doi":"https://doi.org/10.1021/acs.jcim.6b00759","mag":"2604162743","pmid":"https://pubmed.ncbi.nlm.nih.gov/28387522"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.6b00759","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.6b00759","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/A5073149483","display_name":"Silvia Bonomo","orcid":"https://orcid.org/0000-0003-2394-2861"},"institutions":[{"id":"https://openalex.org/I124055696","display_name":"University of Copenhagen","ror":"https://ror.org/035b05819","country_code":"DK","type":"education","lineage":["https://openalex.org/I124055696"]}],"countries":["DK"],"is_corresponding":true,"raw_author_name":"Silvia Bonomo","raw_affiliation_strings":["Department\rof Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen \u00d8, Denmark"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department\rof Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen \u00d8, Denmark","institution_ids":["https://openalex.org/I124055696"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5046853170","display_name":"Flemming Steen J\u00f8rgensen","orcid":"https://orcid.org/0000-0001-8040-2998"},"institutions":[{"id":"https://openalex.org/I124055696","display_name":"University of Copenhagen","ror":"https://ror.org/035b05819","country_code":"DK","type":"education","lineage":["https://openalex.org/I124055696"]}],"countries":["DK"],"is_corresponding":false,"raw_author_name":"Flemming Steen J\u00f8rgensen","raw_affiliation_strings":["Department\rof Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen \u00d8, Denmark"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department\rof Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen \u00d8, Denmark","institution_ids":["https://openalex.org/I124055696"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5002139604","display_name":"Lars Olsen","orcid":"https://orcid.org/0000-0002-7607-7130"},"institutions":[{"id":"https://openalex.org/I124055696","display_name":"University of Copenhagen","ror":"https://ror.org/035b05819","country_code":"DK","type":"education","lineage":["https://openalex.org/I124055696"]}],"countries":["DK"],"is_corresponding":false,"raw_author_name":"Lars Olsen","raw_affiliation_strings":["Department\rof Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen \u00d8, Denmark"],"raw_orcid":"https://orcid.org/0000-0002-7607-7130","affiliations":[{"raw_affiliation_string":"Department\rof Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen \u00d8, Denmark","institution_ids":["https://openalex.org/I124055696"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":["https://openalex.org/A5073149483"],"corresponding_institution_ids":["https://openalex.org/I124055696"],"apc_list":null,"apc_paid":null,"fwci":3.5863,"has_fulltext":false,"cited_by_count":34,"citation_normalized_percentile":{"value":0.91602569,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":90,"max":99},"biblio":{"volume":"57","issue":"5","first_page":"1123","last_page":"1133"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10375","display_name":"Pharmacogenetics and Drug Metabolism","score":0.9998999834060669,"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"}},"topics":[{"id":"https://openalex.org/T10375","display_name":"Pharmacogenetics and Drug Metabolism","score":0.9998999834060669,"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"}},{"id":"https://openalex.org/T10631","display_name":"Cancer, Hypoxia, and Metabolism","score":0.9952999949455261,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"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/T13561","display_name":"Chemical Reactions and Isotopes","score":0.9919000267982483,"subfield":{"id":"https://openalex.org/subfields/3003","display_name":"Pharmaceutical Science"},"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/catalysis","display_name":"Catalysis","score":0.5956604480743408},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.5797759294509888},{"id":"https://openalex.org/keywords/cytochrome-p450","display_name":"Cytochrome P450","score":0.5522336363792419},{"id":"https://openalex.org/keywords/mechanism","display_name":"Mechanism (biology)","score":0.43132591247558594},{"id":"https://openalex.org/keywords/biochemistry","display_name":"Biochemistry","score":0.3962933421134949},{"id":"https://openalex.org/keywords/enzyme","display_name":"Enzyme","score":0.38390204310417175},{"id":"https://openalex.org/keywords/stereochemistry","display_name":"Stereochemistry","score":0.3797970414161682},{"id":"https://openalex.org/keywords/physics","display_name":"Physics","score":0.08611735701560974}],"concepts":[{"id":"https://openalex.org/C161790260","wikidata":"https://www.wikidata.org/wiki/Q82264","display_name":"Catalysis","level":2,"score":0.5956604480743408},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5797759294509888},{"id":"https://openalex.org/C526171541","wikidata":"https://www.wikidata.org/wiki/Q407693","display_name":"Cytochrome P450","level":3,"score":0.5522336363792419},{"id":"https://openalex.org/C89611455","wikidata":"https://www.wikidata.org/wiki/Q6804646","display_name":"Mechanism (biology)","level":2,"score":0.43132591247558594},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.3962933421134949},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.38390204310417175},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.3797970414161682},{"id":"https://openalex.org/C121332964","wikidata":"https://www.wikidata.org/wiki/Q413","display_name":"Physics","level":0,"score":0.08611735701560974},{"id":"https://openalex.org/C62520636","wikidata":"https://www.wikidata.org/wiki/Q944","display_name":"Quantum mechanics","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D002384","descriptor_name":"Catalysis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002384","descriptor_name":"Catalysis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002384","descriptor_name":"Catalysis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006867","descriptor_name":"Hydrolases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D006867","descriptor_name":"Hydrolases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D006867","descriptor_name":"Hydrolases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D006867","descriptor_name":"Hydrolases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D006867","descriptor_name":"Hydrolases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D006867","descriptor_name":"Hydrolases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D008190","descriptor_name":"Lyases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D008190","descriptor_name":"Lyases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D008190","descriptor_name":"Lyases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D008190","descriptor_name":"Lyases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D008190","descriptor_name":"Lyases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D008190","descriptor_name":"Lyases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D013254","descriptor_name":"Steroid 17-alpha-Hydroxylase","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D013254","descriptor_name":"Steroid 17-alpha-Hydroxylase","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D013254","descriptor_name":"Steroid 17-alpha-Hydroxylase","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D013254","descriptor_name":"Steroid 17-alpha-Hydroxylase","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D013254","descriptor_name":"Steroid 17-alpha-Hydroxylase","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D013254","descriptor_name":"Steroid 17-alpha-Hydroxylase","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D015394","descriptor_name":"Molecular Structure","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015394","descriptor_name":"Molecular Structure","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015394","descriptor_name":"Molecular Structure","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D056004","descriptor_name":"Molecular Dynamics Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":4,"locations":[{"id":"doi:10.1021/acs.jcim.6b00759","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.6b00759","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:28387522","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/28387522","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},{"id":"pmh:oai:pure.atira.dk:openaire_cris_publications/f9997edc-8bc7-4729-9a09-7fd2f76f05e8","is_oa":false,"landing_page_url":"https://curis.ku.dk/portal/da/publications/mechanism-of-cytochrome-p450-17a1catalyzed-hydroxylase-and-lyase-reactions(f9997edc-8bc7-4729-9a09-7fd2f76f05e8).html","pdf_url":null,"source":{"id":"https://openalex.org/S4306401983","display_name":"Research at the University of Copenhagen (University of Copenhagen)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I124055696","host_organization_name":"University of Copenhagen","host_organization_lineage":["https://openalex.org/I124055696"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Bonomo , S , J\u00f8rgensen , F S & Olsen , L 2017 , ' Mechanism of Cytochrome P450 17A1-Catalyzed Hydroxylase and Lyase Reactions ' , Journal of Chemical Information and Modeling , vol. 57 , no. 5 , pp. 1123-1133 . https://doi.org/10.1021/acs.jcim.6b00759","raw_type":"article"},{"id":"pmh:oai:pure.atira.dk:publications/f9997edc-8bc7-4729-9a09-7fd2f76f05e8","is_oa":false,"landing_page_url":"https://researchprofiles.ku.dk/da/publications/f9997edc-8bc7-4729-9a09-7fd2f76f05e8","pdf_url":null,"source":{"id":"https://openalex.org/S4306401983","display_name":"Research at the University of Copenhagen (University of Copenhagen)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I124055696","host_organization_name":"University of Copenhagen","host_organization_lineage":["https://openalex.org/I124055696"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Bonomo , S , J\u00f8rgensen , F S & Olsen , L 2017 , ' Mechanism of Cytochrome P450 17A1-Catalyzed Hydroxylase and Lyase Reactions ' , Journal of Chemical Information and Modeling , vol. 57 , no. 5 , pp. 1123-1133 . https://doi.org/10.1021/acs.jcim.6b00759","raw_type":"article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Life in Land","id":"https://metadata.un.org/sdg/15","score":0.4099999964237213}],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":49,"referenced_works":["https://openalex.org/W241512211","https://openalex.org/W1967240005","https://openalex.org/W1970264454","https://openalex.org/W1974254541","https://openalex.org/W1981021420","https://openalex.org/W1982356449","https://openalex.org/W1983935591","https://openalex.org/W1988091937","https://openalex.org/W1989552101","https://openalex.org/W1989555601","https://openalex.org/W1993383767","https://openalex.org/W1999458467","https://openalex.org/W2008145170","https://openalex.org/W2009171847","https://openalex.org/W2014512561","https://openalex.org/W2023271753","https://openalex.org/W2033035711","https://openalex.org/W2035266068","https://openalex.org/W2040153399","https://openalex.org/W2042939317","https://openalex.org/W2043757280","https://openalex.org/W2045683699","https://openalex.org/W2048946635","https://openalex.org/W2050456292","https://openalex.org/W2055563809","https://openalex.org/W2067873880","https://openalex.org/W2069053623","https://openalex.org/W2072206903","https://openalex.org/W2078146328","https://openalex.org/W2092157292","https://openalex.org/W2100032379","https://openalex.org/W2106050611","https://openalex.org/W2111816290","https://openalex.org/W2112100343","https://openalex.org/W2114042189","https://openalex.org/W2117000356","https://openalex.org/W2119292856","https://openalex.org/W2126733133","https://openalex.org/W2128572087","https://openalex.org/W2141068637","https://openalex.org/W2143981217","https://openalex.org/W2144288821","https://openalex.org/W2144999739","https://openalex.org/W2204191294","https://openalex.org/W2303298430","https://openalex.org/W2319340717","https://openalex.org/W2461552319","https://openalex.org/W2471994454","https://openalex.org/W2943419509"],"related_works":["https://openalex.org/W4391375266","https://openalex.org/W2092275170","https://openalex.org/W3193749472","https://openalex.org/W1967978480","https://openalex.org/W1974837029","https://openalex.org/W2760087092","https://openalex.org/W3092177084","https://openalex.org/W3157340793","https://openalex.org/W2009067244","https://openalex.org/W3125507250"],"abstract_inverted_index":{"Cytochrome":[0],"P450":[1],"17A1":[2],"(CYP17A1)":[3],"catalyzes":[4],"C17":[5,142],"hydroxylation":[6,143,195],"of":[7,107,134,172,208,222,239,245],"pregnenolone":[8],"and":[9,11,27,49,58,81,110,182],"progesterone":[10],"the":[12,32,36,42,47,59,101,121,127,131,138,141,152,155,164,169,173,179,186,194,198,205,217,220,223,232,237,243,246],"subsequent":[13],"C17\u2013C20":[14],"bond":[15],"cleavage":[16],"(lyase":[17],"reaction)":[18],"to":[19,72,78,85,145,189,236],"form":[20],"androgen":[21],"precursors.":[22],"Compound":[23],"I":[24,181],"(Cpd":[25],"I)":[26],"peroxo":[28],"anion":[29],"(POA)":[30],"are":[31],"heme-reactive":[33],"species":[34],"underlying":[35],"two":[37,104,128],"reactions.":[38],"We":[39],"have":[40,75],"characterized":[41],"reaction":[43,74,158],"path":[44],"for":[45,69,92,126,140,154,193,204,210],"both":[46,177],"hydroxylase":[48,73],"lyase":[50,102,157],"reactions":[51,129],"using":[52],"density":[53],"functional":[54],"theory":[55],"(DFT)":[56],"calculations":[57],"enzyme\u2013substrate":[60],"interactions":[61,230],"by":[62,148,228],"molecular":[63],"dynamics":[64],"(MD)":[65],"simulations.":[66],"Activation":[67],"barriers":[68],"positions":[70],"subject":[71],"values":[76],"close":[77],"each":[79],"other":[80],"span":[82],"from":[83],"54":[84],"60":[86],"kJ\u00b7mol\u20131":[87],"with":[88,97,112,185,231],"a":[89,201],"small":[90],"preference":[91],"17\u03b1":[93],"hydroxylation,":[94],"in":[95,163,168,178,234],"agreement":[96],"experimental":[98],"observations.":[99],"For":[100],"reaction,":[103],"different":[105],"types":[106],"mechanisms,":[108],"concerted":[109],"stepwise,":[111],"identical":[113],"activation":[114],"energies":[115],"(87":[116],"kJ\u00b7mol\u20131)":[117],"were":[118,175],"identified.":[119],"Embedding":[120],"DFT-optimized":[122],"transition":[123],"states":[124],"(TSs)":[125],"into":[130],"active":[132],"site":[133,196],"CYP17A1":[135,209],"showed":[136],"that":[137,219],"TS":[139,153],"needs":[144],"be":[146,161,190],"distorted":[147],"13":[149],"kJ\u00b7mol\u20131,":[150],"whereas":[151],"17,20":[156],"easily":[159],"can":[160],"accommodated":[162],"protein.":[165],"Finally,":[166],"differences":[167],"hydrogen-bond":[170],"pattern":[171],"substrates":[174,247],"detected":[176],"CYP17A1\u2013Cpd":[180],"CYP17A1\u2013POA":[183],"complexes,":[184],"former":[187],"found":[188],"more":[191],"pivotal":[192],"than":[197],"latter,":[199],"suggesting":[200],"possible":[202],"explanation":[203],"slower":[206],"conversion":[207],"17\u03b1-hydroxyprogesterone":[211],"over":[212],"17\u03b1-hydroxypregnenolone.":[213],"The":[214],"results":[215],"support":[216],"concept":[218],"selectivity":[221,238],"steroidogenic":[224],"CYPs":[225],"is":[226],"ruled":[227],"direct":[229],"enzyme,":[233],"contrast":[235],"drug-metabolizing":[240],"CYPs,":[241],"where":[242],"reactivity":[244],"dominates.":[248]},"counts_by_year":[{"year":2026,"cited_by_count":3},{"year":2025,"cited_by_count":4},{"year":2024,"cited_by_count":2},{"year":2023,"cited_by_count":5},{"year":2022,"cited_by_count":1},{"year":2021,"cited_by_count":6},{"year":2020,"cited_by_count":3},{"year":2019,"cited_by_count":3},{"year":2018,"cited_by_count":4},{"year":2017,"cited_by_count":3}],"updated_date":"2026-05-16T08:24:45.110214","created_date":"2025-10-10T00:00:00"}