{"id":"https://openalex.org/W7223051667","doi":"https://doi.org/10.64898/2026.10.19.760170","title":"Dual-portal ligand transport in human cytochrome P450 17A1","display_name":"Dual-portal ligand transport in human cytochrome P450 17A1","publication_year":2026,"publication_date":"2026-10-20","ids":{"openalex":"https://openalex.org/W7223051667","doi":"https://doi.org/10.64898/2026.10.19.760170"},"language":"en","primary_location":{"id":"doi:10.64898/2026.10.19.760170","doi":"https://doi.org/10.64898/2026.10.19.760170","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.19.760170","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/20/2026.10.19.760170.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/20/2026.10.19.760170.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5113419293","display_name":"Yingtong Xu","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I118564535","display_name":"University of Bern","ror":"https://ror.org/02k7v4d05","country_code":"CH","type":"education","lineage":["https://openalex.org/I118564535"]},{"id":"https://openalex.org/I2801112126","display_name":"University Hospital of Bern","ror":"https://ror.org/01q9sj412","country_code":"CH","type":"healthcare","lineage":["https://openalex.org/I2801112126"]},{"id":"https://openalex.org/I4210122458","display_name":"University Children\u2019s Hospital Bern","ror":"https://ror.org/02k9jrs03","country_code":"CH","type":"healthcare","lineage":["https://openalex.org/I2801112126","https://openalex.org/I4210122458"]}],"countries":["CH"],"is_corresponding":false,"raw_author_name":"Yingtong Xu","raw_affiliation_strings":["Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland","Pediatric Endocrinology, Diabetology and Metabolism, University Children\u2019s Hospital, Inselspital, Bern, Switzerland","Translational Hormone Research Program, Department of Biomedical Research, Faculty of Medicine, University of Bern, Bern, Switzerland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland","institution_ids":["https://openalex.org/I118564535"]},{"raw_affiliation_string":"Pediatric Endocrinology, Diabetology and Metabolism, University Children\u2019s Hospital, Inselspital, Bern, Switzerland","institution_ids":["https://openalex.org/I2801112126","https://openalex.org/I4210122458"]},{"raw_affiliation_string":"Translational Hormone Research Program, Department of Biomedical Research, Faculty of Medicine, University of Bern, Bern, Switzerland","institution_ids":["https://openalex.org/I118564535"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5159112375","display_name":"Adam Zawlewski","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I118564535","display_name":"University of Bern","ror":"https://ror.org/02k7v4d05","country_code":"CH","type":"education","lineage":["https://openalex.org/I118564535"]},{"id":"https://openalex.org/I2801112126","display_name":"University Hospital of Bern","ror":"https://ror.org/01q9sj412","country_code":"CH","type":"healthcare","lineage":["https://openalex.org/I2801112126"]},{"id":"https://openalex.org/I4210122458","display_name":"University Children\u2019s Hospital Bern","ror":"https://ror.org/02k9jrs03","country_code":"CH","type":"healthcare","lineage":["https://openalex.org/I2801112126","https://openalex.org/I4210122458"]}],"countries":["CH"],"is_corresponding":false,"raw_author_name":"Adam Zalewski","raw_affiliation_strings":["Pediatric Endocrinology, Diabetology and Metabolism, University Children\u2019s Hospital, Inselspital, Bern, Switzerland","Translational Hormone Research Program, Department of Biomedical Research, Faculty of Medicine, University of Bern, Bern, Switzerland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Pediatric Endocrinology, Diabetology and Metabolism, University Children\u2019s Hospital, Inselspital, Bern, Switzerland","institution_ids":["https://openalex.org/I2801112126","https://openalex.org/I4210122458"]},{"raw_affiliation_string":"Translational Hormone Research Program, Department of Biomedical Research, Faculty of Medicine, University of Bern, Bern, Switzerland","institution_ids":["https://openalex.org/I118564535"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5024262855","display_name":"Amit V. Pandey","orcid":"https://orcid.org/0000-0001-8331-5902","observed_orcids":["https://orcid.org/0000-0001-8331-5902"]},"institutions":[{"id":"https://openalex.org/I118564535","display_name":"University of Bern","ror":"https://ror.org/02k7v4d05","country_code":"CH","type":"education","lineage":["https://openalex.org/I118564535"]},{"id":"https://openalex.org/I2801112126","display_name":"University Hospital of Bern","ror":"https://ror.org/01q9sj412","country_code":"CH","type":"healthcare","lineage":["https://openalex.org/I2801112126"]},{"id":"https://openalex.org/I4210122458","display_name":"University Children\u2019s Hospital Bern","ror":"https://ror.org/02k9jrs03","country_code":"CH","type":"healthcare","lineage":["https://openalex.org/I2801112126","https://openalex.org/I4210122458"]}],"countries":["CH"],"is_corresponding":true,"raw_author_name":"Amit V. Pandey","raw_affiliation_strings":["Department of Digital Medicine, University of Bern, 3008 Bern, Switzerland","Pediatric Endocrinology, Diabetology and Metabolism, University Children\u2019s Hospital, Inselspital, Bern, Switzerland","Translational Hormone Research Program, Department of Biomedical Research, Faculty of Medicine, University of Bern, Bern, Switzerland"],"raw_orcid":"https://orcid.org/0000-0001-8331-5902","affiliations":[{"raw_affiliation_string":"Department of Digital Medicine, University of Bern, 3008 Bern, Switzerland","institution_ids":["https://openalex.org/I118564535"]},{"raw_affiliation_string":"Pediatric Endocrinology, Diabetology and Metabolism, University Children\u2019s Hospital, Inselspital, Bern, Switzerland","institution_ids":["https://openalex.org/I2801112126","https://openalex.org/I4210122458"]},{"raw_affiliation_string":"Translational Hormone Research Program, Department of Biomedical Research, Faculty of Medicine, University of Bern, Bern, Switzerland","institution_ids":["https://openalex.org/I118564535"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":["https://openalex.org/A5024262855"],"corresponding_institution_ids":["https://openalex.org/I118564535","https://openalex.org/I2801112126","https://openalex.org/I4210122458"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10044","display_name":"Protein Structure and Dynamics","score":0.5429999828338623,"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/T10044","display_name":"Protein Structure and Dynamics","score":0.5429999828338623,"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/T11747","display_name":"Metal-Catalyzed Oxygenation Mechanisms","score":0.12250000238418579,"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/T11162","display_name":"Enzyme Structure and Function","score":0.1080000028014183,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/cyp17a1","display_name":"CYP17A1","score":0.9729999899864197},{"id":"https://openalex.org/keywords/cytochrome-p450-17a1","display_name":"cytochrome P450 17A1","score":0.906000018119812},{"id":"https://openalex.org/keywords/steroidogenesis","display_name":"steroidogenesis","score":0.6980000138282776},{"id":"https://openalex.org/keywords/vectorial-transport","display_name":"vectorial transport","score":0.6420000195503235},{"id":"https://openalex.org/keywords/17alpha-hydroxylation","display_name":"17\u03b1-hydroxylation","score":0.890999972820282},{"id":"https://openalex.org/keywords/17-20-lyase","display_name":"17,20-lyase","score":0.9100000262260437},{"id":"https://openalex.org/keywords/abiraterone-acetate","display_name":"abiraterone","score":0.8389999866485596},{"id":"https://openalex.org/keywords/molecular-dynamics","display_name":"molecular dynamics","score":0.6460000276565552},{"id":"https://openalex.org/keywords/site-directed-mutagenesis","display_name":"site-directed mutagenesis","score":0.7250000238418579}],"concepts":[{"id":"https://openalex.org/C142716871","wikidata":"https://www.wikidata.org/wiki/Q408305","display_name":"CYP17A1","level":3,"score":0.8083999752998352},{"id":"https://openalex.org/C41183919","wikidata":"https://www.wikidata.org/wiki/Q423026","display_name":"Active site","level":3,"score":0.6373000144958496},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5558000206947327},{"id":"https://openalex.org/C116569031","wikidata":"https://www.wikidata.org/wiki/Q899107","display_name":"Ligand (biochemistry)","level":3,"score":0.4936000108718872},{"id":"https://openalex.org/C158617107","wikidata":"https://www.wikidata.org/wiki/Q79927","display_name":"Endoplasmic reticulum","level":2,"score":0.47609999775886536},{"id":"https://openalex.org/C526171541","wikidata":"https://www.wikidata.org/wiki/Q407693","display_name":"Cytochrome P450","level":3,"score":0.4246000051498413},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.3970000147819519},{"id":"https://openalex.org/C175656101","wikidata":"https://www.wikidata.org/wiki/Q56646","display_name":"Chinese hamster ovary cell","level":3,"score":0.3781000077724457},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.35899999737739563},{"id":"https://openalex.org/C174510640","wikidata":"https://www.wikidata.org/wiki/Q489618","display_name":"HEK 293 cells","level":3,"score":0.3492000102996826},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.3463999927043915},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.3321000039577484},{"id":"https://openalex.org/C175156509","wikidata":"https://www.wikidata.org/wiki/Q1990218","display_name":"Cleavage (geology)","level":3,"score":0.3082999885082245},{"id":"https://openalex.org/C2775905019","wikidata":"https://www.wikidata.org/wiki/Q192572","display_name":"In silico","level":3,"score":0.2996000051498413},{"id":"https://openalex.org/C41685203","wikidata":"https://www.wikidata.org/wiki/Q1974042","display_name":"Docking (animal)","level":2,"score":0.29429998993873596},{"id":"https://openalex.org/C87644729","wikidata":"https://www.wikidata.org/wiki/Q547502","display_name":"Microsome","level":3,"score":0.27720001339912415},{"id":"https://openalex.org/C2779343474","wikidata":"https://www.wikidata.org/wiki/Q3109175","display_name":"Context (archaeology)","level":2,"score":0.2720000147819519},{"id":"https://openalex.org/C2779384962","wikidata":"https://www.wikidata.org/wiki/Q5201346","display_name":"Cytochrome b5","level":4,"score":0.2700999975204468},{"id":"https://openalex.org/C57581600","wikidata":"https://www.wikidata.org/wiki/Q2449730","display_name":"Transport protein","level":2,"score":0.26510000228881836},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.2630999982357025},{"id":"https://openalex.org/C207583985","wikidata":"https://www.wikidata.org/wiki/Q128723","display_name":"Wild type","level":4,"score":0.2572000026702881},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.2554999887943268}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.10.19.760170","doi":"https://doi.org/10.64898/2026.10.19.760170","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.19.760170","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/20/2026.10.19.760170.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.10.19.760170","doi":"https://doi.org/10.64898/2026.10.19.760170","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.19.760170","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/20/2026.10.19.760170.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.5683000087738037,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7223051667.pdf","grobid_xml":"https://content.openalex.org/works/W7223051667.grobid-xml"},"referenced_works_count":39,"referenced_works":["https://openalex.org/W1963514652","https://openalex.org/W1968973920","https://openalex.org/W1995802297","https://openalex.org/W2009171847","https://openalex.org/W2014512561","https://openalex.org/W2019519304","https://openalex.org/W2020601379","https://openalex.org/W2024092408","https://openalex.org/W2030859870","https://openalex.org/W2038530231","https://openalex.org/W2069518737","https://openalex.org/W2079050871","https://openalex.org/W2083768732","https://openalex.org/W2083967315","https://openalex.org/W2110534364","https://openalex.org/W2126733133","https://openalex.org/W2137825366","https://openalex.org/W2144874144","https://openalex.org/W2144999739","https://openalex.org/W2170544517","https://openalex.org/W2415807962","https://openalex.org/W2462797823","https://openalex.org/W2587450560","https://openalex.org/W2604798886","https://openalex.org/W2725904614","https://openalex.org/W2750662929","https://openalex.org/W2802276497","https://openalex.org/W2804253674","https://openalex.org/W2807292831","https://openalex.org/W3135589815","https://openalex.org/W3148246805","https://openalex.org/W4376641607","https://openalex.org/W4402898197","https://openalex.org/W4404642664","https://openalex.org/W4407579752","https://openalex.org/W4409598151","https://openalex.org/W7153770601","https://openalex.org/W7163739563","https://openalex.org/W7220377448"],"related_works":["https://openalex.org/W4387379905","https://openalex.org/W2518031329","https://openalex.org/W3174210032","https://openalex.org/W2604798886","https://openalex.org/W1455240055","https://openalex.org/W3148246805","https://openalex.org/W4315476317","https://openalex.org/W2122704575","https://openalex.org/W2014512561","https://openalex.org/W2604162743"],"abstract_inverted_index":{"Abstract":[0],"Human":[1],"cytochrome":[2],"P450":[3],"17A1":[4],"(CYP17A1)":[5],"is":[6,24],"the":[7,25,28,51,57,68,73,85,103,135,165,186,199],"qualitative":[8],"regulator":[9],"of":[10,27,78,84,119,198,207,227],"steroidogenesis,":[11],"catalyzing":[12],"both":[13,127,141],"17\u03b1-hydroxylation":[14],"and":[15,23,41,76,126,129,144,174,213],"17,20-lyase":[16],"cleavage":[17],"at":[18],"a":[19,224],"single":[20],"active":[21,70],"site,":[22],"target":[26],"prostate":[29],"cancer":[30],"drug":[31],"abiraterone.":[32],"Crystal":[33],"structures":[34],"show":[35],"an":[36,181],"almost":[37],"fully":[38],"enclosed":[39],"site":[40,71],"do":[42],"not":[43],"reveal":[44],"how":[45,56],"lipophilic":[46],"steroids":[47],"reach":[48],"it":[49],"from":[50],"endoplasmic":[52],"reticulum":[53],"membrane":[54],"or":[55],"more":[58],"polar":[59],"products":[60],"leave.":[61],"We":[62],"therefore":[63],"asked":[64],"which":[65,77,100],"routes":[66],"connect":[67],"CYP17A1":[69,86,120,214],"to":[72,114],"protein":[74,215],"surface,":[75],"them":[79,147],"are":[80],"required.":[81],"Molecular":[82],"dynamics":[83],"enzyme":[87],"followed":[88],"by":[89,102],"CAVER":[90],"tunnel":[91],"clustering":[92],"produced":[93],"99":[94],"transport":[95,230],"pathways":[96],"in":[97,123,164,231],"14":[98],"clusters,":[99],"grouped":[101],"elements":[104],"forming":[105],"their":[106],"mouths":[107],"into":[108],"four":[109],"topologically":[110],"distinct":[111],"portals":[112],"(P-I":[113],"P-IV).":[115],"Five":[116],"structure-guided":[117],"variants":[118],"were":[121,132],"expressed":[122],"HEK293":[124],"cells":[125],"hydroxylase":[128],"lyase":[130],"reactions":[131,142],"measured.":[133],"Occluding":[134],"dominant":[136],"P-I/P-II":[137],"bottleneck":[138],"(A105L)":[139],"left":[140],"intact":[143],"slightly":[145],"raised":[146],"(116.1":[148],"\u00b1":[149,156,172,176],"8.0%":[150],"hydroxylase,":[151],"P":[152,159,193],"=":[153,160],"0.0043;":[154],"134.8":[155],"27.9%":[157],"lyase,":[158],"0.028).":[161],"A":[162],"tryptophan":[163],"F/G":[166],"lumen":[167],"(L242W)":[168],"was":[169],"tolerated":[170],"(96.6":[171],"6.9%":[173],"89.9":[175],"10.4%,":[177],"neither":[178,219],"significant),":[179],"whereas":[180],"engineered":[182],"I205C/R239C":[183],"pair":[184],"across":[185],"same":[187],"route":[188],"abolished":[189],"catalysis":[190],"(below":[191],"2%,":[192],"<":[194,211],"0.001).":[195],"Both":[196],"perturbations":[197],"membrane-facing":[200],"P-IV":[201],"portal":[202],"cut":[203],"activity":[204],"below":[205],"2%":[206],"wild":[208],"type":[209],"(P":[210],"0.001),":[212],"levels":[216],"accounted":[217],"for":[218],"phenotype.":[220],"These":[221],"data":[222],"support":[223],"dual-portal":[225],"model":[226],"vectorial":[228],"ligand":[229],"CYP17A1.":[232]},"counts_by_year":[],"updated_date":"2026-10-28T10:33:24.094632","created_date":"2026-10-21T00:00:00"}