{"id":"https://openalex.org/W4387089883","doi":"https://doi.org/10.1158/1535-7163.mct-23-0358","title":"Structural Insight into Geranylgeranyl Diphosphate Synthase (GGDPS) for Cancer Therapy","display_name":"Structural Insight into Geranylgeranyl Diphosphate Synthase (GGDPS) for Cancer Therapy","publication_year":2023,"publication_date":"2023-09-26","ids":{"openalex":"https://openalex.org/W4387089883","doi":"https://doi.org/10.1158/1535-7163.mct-23-0358","pmid":"https://pubmed.ncbi.nlm.nih.gov/37756579","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/10762340"},"language":"en","primary_location":{"id":"doi:10.1158/1535-7163.mct-23-0358","doi":"https://doi.org/10.1158/1535-7163.mct-23-0358","is_oa":true,"landing_page_url":"https://doi.org/10.1158/1535-7163.mct-23-0358","pdf_url":"https://aacrjournals.org/mct/article-pdf/doi/10.1158/1535-7163.MCT-23-0358/3367357/mct-23-0358.pdf","source":{"id":"https://openalex.org/S48437117","display_name":"Molecular Cancer Therapeutics","issn_l":"1535-7163","issn":["1535-7163","1538-8514"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Molecular Cancer Therapeutics","raw_type":"journal-article"},"volume":null,"type":"review","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"hybrid","oa_url":"https://aacrjournals.org/mct/article-pdf/doi/10.1158/1535-7163.MCT-23-0358/3367357/mct-23-0358.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5020406987","display_name":"Andrew C. Pham","orcid":"https://orcid.org/0009-0008-7901-9746","observed_orcids":["https://orcid.org/0009-0008-7901-9746"]},"institutions":[{"id":"https://openalex.org/I59130452","display_name":"University of Nebraska Medical Center","ror":"https://ror.org/00thqtb16","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I59130452"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Andrew C. Pham","raw_affiliation_strings":["1Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska"],"raw_orcid":"https://orcid.org/0009-0008-7901-9746","affiliations":[{"raw_affiliation_string":"1Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska","institution_ids":["https://openalex.org/I59130452"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5005732386","display_name":"Sarah A. Holstein","orcid":"https://orcid.org/0000-0002-9342-5635","observed_orcids":["https://orcid.org/0000-0002-9342-5635"]},"institutions":[{"id":"https://openalex.org/I59130452","display_name":"University of Nebraska Medical Center","ror":"https://ror.org/00thqtb16","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I59130452"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Sarah A. Holstein","raw_affiliation_strings":["2Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska"],"raw_orcid":"https://orcid.org/0000-0002-9342-5635","affiliations":[{"raw_affiliation_string":"2Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska","institution_ids":["https://openalex.org/I59130452"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5158861295","display_name":"Gloria E.O. Borgstahl","orcid":"https://orcid.org/0000-0001-8070-0258","observed_orcids":["https://orcid.org/0000-0001-8070-0258"]},"institutions":[{"id":"https://openalex.org/I59130452","display_name":"University of Nebraska Medical Center","ror":"https://ror.org/00thqtb16","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I59130452"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Gloria E.O. Borgstahl","raw_affiliation_strings":["1Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska","3The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska"],"raw_orcid":"https://orcid.org/0000-0001-8070-0258","affiliations":[{"raw_affiliation_string":"1Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska","institution_ids":["https://openalex.org/I59130452"]},{"raw_affiliation_string":"3The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska","institution_ids":["https://openalex.org/I59130452"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5158861295"],"corresponding_institution_ids":["https://openalex.org/I59130452"],"apc_list":null,"apc_paid":null,"fwci":0.2373,"has_fulltext":true,"cited_by_count":9,"citation_normalized_percentile":{"value":0.21943128,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":98},"biblio":{"volume":"23","issue":"1","first_page":"14","last_page":"23"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11882","display_name":"Plant biochemistry and biosynthesis","score":0.4235999882221222,"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/T11882","display_name":"Plant biochemistry and biosynthesis","score":0.4235999882221222,"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/T10169","display_name":"Protein Kinase Regulation and GTPase Signaling","score":0.1664000004529953,"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/T11162","display_name":"Enzyme Structure and Function","score":0.13650000095367432,"subfield":{"id":"https://openalex.org/subfields/2505","display_name":"Materials Chemistry"},"field":{"id":"https://openalex.org/fields/25","display_name":"Materials Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/geranylgeranyl-diphosphate-synthase","display_name":"geranylgeranyl diphosphate synthase","score":0.9990000128746033},{"id":"https://openalex.org/keywords/protein-geranylgeranylation","display_name":"protein geranylgeranylation","score":0.8539999723434448},{"id":"https://openalex.org/keywords/isoprenoid-metabolism","display_name":"isoprenoid metabolism","score":0.7409999966621399},{"id":"https://openalex.org/keywords/anticancer-drug-targets","display_name":"anticancer drug targets","score":0.8500000238418579},{"id":"https://openalex.org/keywords/enzyme-structure","display_name":"enzyme structure","score":0.7590000033378601},{"id":"https://openalex.org/keywords/active-site","display_name":"active site","score":0.7179999947547913},{"id":"https://openalex.org/keywords/electrostatic-surface","display_name":"electrostatic surface","score":0.8009999990463257},{"id":"https://openalex.org/keywords/structure-based-drug-design","display_name":"structure-based drug design","score":0.8090000152587891}],"concepts":[{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5494274497032166},{"id":"https://openalex.org/C107824862","wikidata":"https://www.wikidata.org/wiki/Q616005","display_name":"Binding site","level":2,"score":0.4560541808605194},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.4486869275569916},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.4461204707622528},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.4330238103866577},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.42514389753341675},{"id":"https://openalex.org/C2983331546","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer therapy","level":3,"score":0.4218190610408783},{"id":"https://openalex.org/C41183919","wikidata":"https://www.wikidata.org/wiki/Q423026","display_name":"Active site","level":3,"score":0.41541358828544617},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.3575776219367981},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.33265477418899536},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.255007803440094},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.21177524328231812},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D004791","descriptor_name":"Enzyme Inhibitors","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D004791","descriptor_name":"Enzyme Inhibitors","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":true},{"descriptor_ui":"D004791","descriptor_name":"Enzyme Inhibitors","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009369","descriptor_name":"Neoplasms","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D013729","descriptor_name":"Terpenes","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D013729","descriptor_name":"Terpenes","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D017368","descriptor_name":"Protein Prenylation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051231","descriptor_name":"Farnesyltranstransferase","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D051231","descriptor_name":"Farnesyltranstransferase","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false}],"locations_count":3,"locations":[{"id":"doi:10.1158/1535-7163.mct-23-0358","doi":"https://doi.org/10.1158/1535-7163.mct-23-0358","is_oa":true,"landing_page_url":"https://doi.org/10.1158/1535-7163.mct-23-0358","pdf_url":"https://aacrjournals.org/mct/article-pdf/doi/10.1158/1535-7163.MCT-23-0358/3367357/mct-23-0358.pdf","source":{"id":"https://openalex.org/S48437117","display_name":"Molecular Cancer Therapeutics","issn_l":"1535-7163","issn":["1535-7163","1538-8514"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Molecular Cancer Therapeutics","raw_type":"journal-article"},{"id":"pmh:oai:pubmedcentral.nih.gov:10762340","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10762340","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"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":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Mol Cancer Ther","raw_type":"Text"},{"id":"pmid:37756579","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/37756579","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":"Molecular cancer therapeutics","raw_type":"Review"}],"best_oa_location":{"id":"doi:10.1158/1535-7163.mct-23-0358","doi":"https://doi.org/10.1158/1535-7163.mct-23-0358","is_oa":true,"landing_page_url":"https://doi.org/10.1158/1535-7163.mct-23-0358","pdf_url":"https://aacrjournals.org/mct/article-pdf/doi/10.1158/1535-7163.MCT-23-0358/3367357/mct-23-0358.pdf","source":{"id":"https://openalex.org/S48437117","display_name":"Molecular Cancer Therapeutics","issn_l":"1535-7163","issn":["1535-7163","1538-8514"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Molecular Cancer Therapeutics","raw_type":"journal-article"},"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.6240000128746033}],"study_designs":[],"awards":[{"id":"https://openalex.org/G4482103134","display_name":null,"funder_award_id":"P200A210032","funder_id":"https://openalex.org/F4320306106","funder_display_name":"U.S. Department of Education"},{"id":"https://openalex.org/G7676807519","display_name":"Nebraska Research Network in Functional Genomics","funder_award_id":"P20GM103427","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"},{"id":"https://openalex.org/G9000859617","display_name":"Geranylgeranyl diphosphate synthase inhibitor therapy for multiple myeloma","funder_award_id":"R01CA258621","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"},{"id":"https://openalex.org/G9000903950","display_name":"Buffett Cancer Center Support Grant","funder_award_id":"P30CA036727","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"}],"funders":[{"id":"https://openalex.org/F4320306106","display_name":"U.S. Department of Education","ror":"https://ror.org/021adze67"},{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"},{"id":"https://openalex.org/F4320337351","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81"},{"id":"https://openalex.org/F4320337354","display_name":"National Institute of General Medical Sciences","ror":"https://ror.org/04q48ey07"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W4387089883.pdf","grobid_xml":"https://content.openalex.org/works/W4387089883.grobid-xml"},"referenced_works_count":87,"referenced_works":["https://openalex.org/W569623023","https://openalex.org/W1481147497","https://openalex.org/W1498067249","https://openalex.org/W1898860290","https://openalex.org/W1970336360","https://openalex.org/W1970757070","https://openalex.org/W1972514452","https://openalex.org/W1972665180","https://openalex.org/W1993573607","https://openalex.org/W2001149281","https://openalex.org/W2002831116","https://openalex.org/W2010316877","https://openalex.org/W2024350208","https://openalex.org/W2026642838","https://openalex.org/W2028816469","https://openalex.org/W2029178634","https://openalex.org/W2033933079","https://openalex.org/W2041288377","https://openalex.org/W2041713157","https://openalex.org/W2042066399","https://openalex.org/W2051839246","https://openalex.org/W2059471644","https://openalex.org/W2062487023","https://openalex.org/W2065731309","https://openalex.org/W2074370114","https://openalex.org/W2075982708","https://openalex.org/W2086326768","https://openalex.org/W2090766575","https://openalex.org/W2104717964","https://openalex.org/W2104788669","https://openalex.org/W2107272456","https://openalex.org/W2111778006","https://openalex.org/W2120772351","https://openalex.org/W2124166505","https://openalex.org/W2134402164","https://openalex.org/W2134567993","https://openalex.org/W2152704187","https://openalex.org/W2171745736","https://openalex.org/W2173594933","https://openalex.org/W2173920250","https://openalex.org/W2176744910","https://openalex.org/W2272329318","https://openalex.org/W2400174168","https://openalex.org/W2411247746","https://openalex.org/W2416133798","https://openalex.org/W2416551856","https://openalex.org/W2418655176","https://openalex.org/W2507482501","https://openalex.org/W2519615309","https://openalex.org/W2531808256","https://openalex.org/W2568935303","https://openalex.org/W2592769203","https://openalex.org/W2595539895","https://openalex.org/W2625828839","https://openalex.org/W2734510265","https://openalex.org/W2747641745","https://openalex.org/W2767018074","https://openalex.org/W2793186466","https://openalex.org/W2796336382","https://openalex.org/W2884528442","https://openalex.org/W2893554229","https://openalex.org/W2898293688","https://openalex.org/W2922471476","https://openalex.org/W2923695679","https://openalex.org/W2948831670","https://openalex.org/W2953016882","https://openalex.org/W2968520866","https://openalex.org/W2968919405","https://openalex.org/W2969489841","https://openalex.org/W2969625719","https://openalex.org/W2975957844","https://openalex.org/W2991090734","https://openalex.org/W3010233577","https://openalex.org/W3012637457","https://openalex.org/W3133919852","https://openalex.org/W3139175283","https://openalex.org/W3177499002","https://openalex.org/W3177828909","https://openalex.org/W3200317384","https://openalex.org/W4226359203","https://openalex.org/W4280588241","https://openalex.org/W4293364222","https://openalex.org/W4310022409","https://openalex.org/W4313654640","https://openalex.org/W4317358994","https://openalex.org/W4378746087","https://openalex.org/W6714802605"],"related_works":["https://openalex.org/W2617906859","https://openalex.org/W2418655176","https://openalex.org/W7222460580","https://openalex.org/W2568935303","https://openalex.org/W2001387572","https://openalex.org/W7136043416","https://openalex.org/W4317358994","https://openalex.org/W7097584793","https://openalex.org/W7101392210","https://openalex.org/W2592769203"],"abstract_inverted_index":{"Geranylgeranyl":[0],"diphosphate":[1],"synthase":[2],"(GGDPS),":[3],"the":[4,7,24,38,52,94,102,110,116],"source":[5],"of":[6,26,42,69,89,96,112],"isoprenoid":[8],"donor":[9],"in":[10],"protein":[11],"geranylgeranylation":[12],"reactions,":[13],"has":[14],"become":[15],"an":[16],"attractive":[17],"target":[18],"for":[19,126],"anticancer":[20],"therapy":[21],"due":[22],"to":[23,84],"reliance":[25],"cancers":[27],"on":[28,36],"geranylgeranylated":[29],"proteins.":[30],"Current":[31],"GGDPS":[32,48,77],"inhibitor":[33,49,107,129],"development":[34],"focuses":[35],"optimizing":[37,128],"drug-target":[39],"enzyme":[40,53],"interactions":[41,59],"nitrogen-containing":[43],"bisphosphonate-based":[44],"drugs.":[45],"To":[46],"advance":[47],"development,":[50],"understanding":[51],"structure,":[54],"active":[55],"site,":[56],"and":[57,75,79,105,131],"ligand/product":[58],"is":[60],"essential.":[61],"Here":[62],"we":[63],"provide":[64],"a":[65,123],"comprehensive":[66],"structure-focused":[67],"review":[68],"GGDPS.":[70],"We":[71,92],"reviewed":[72],"available":[73],"yeast":[74],"human":[76],"structures":[78],"then":[80],"used":[81],"AlphaFold":[82],"modeling":[83],"complete":[85],"unsolved":[86],"structural":[87],"aspects":[88],"these":[90],"models.":[91],"delineate":[93],"elements":[95],"higher-order":[97],"structure":[98],"formation,":[99],"product-substrate":[100],"binding,":[101],"electrostatic":[103],"surface,":[104],"small-molecule":[106],"binding.":[108],"With":[109],"rise":[111],"structure-based":[113],"drug":[114],"design,":[115],"information":[117],"provided":[118],"here":[119],"will":[120],"serve":[121],"as":[122],"valuable":[124],"tool":[125],"rationally":[127],"selectivity":[130],"effectiveness.":[132]},"counts_by_year":[{"year":2026,"cited_by_count":4},{"year":2025,"cited_by_count":4},{"year":2024,"cited_by_count":1}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2023-09-28T00:00:00"}
