{"id":"https://openalex.org/W2015667278","doi":"https://doi.org/10.1073/pnas.93.9.4316","title":"Didemnin binds to the protein palmitoyl thioesterase responsible for infantile neuronal ceroid lipofuscinosis.","display_name":"Didemnin binds to the protein palmitoyl thioesterase responsible for infantile neuronal ceroid lipofuscinosis.","publication_year":1996,"publication_date":"1996-04-30","ids":{"openalex":"https://openalex.org/W2015667278","doi":"https://doi.org/10.1073/pnas.93.9.4316","mag":"2015667278","pmid":"https://pubmed.ncbi.nlm.nih.gov/8633062","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/39533"},"language":"en","primary_location":{"id":"doi:10.1073/pnas.93.9.4316","doi":"https://doi.org/10.1073/pnas.93.9.4316","is_oa":false,"landing_page_url":"https://doi.org/10.1073/pnas.93.9.4316","pdf_url":null,"source":{"id":"https://openalex.org/S125754415","display_name":"Proceedings of the National Academy of Sciences","issn_l":"0027-8424","issn":["0027-8424","1091-6490"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-a","doyens","erih-plus","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320052","host_organization_name":"National Academy of Sciences","host_organization_lineage":["https://openalex.org/P4310320052"],"host_organization_lineage_names":["National Academy of Sciences"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Proceedings of the National Academy of Sciences","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"http://europepmc.org/pmc/articles/PMC39533","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5016866989","display_name":"Craig M. Crews","orcid":"https://orcid.org/0000-0002-8456-2005","observed_orcids":["https://orcid.org/0000-0002-8456-2005"]},"institutions":[{"id":"https://openalex.org/I1344073410","display_name":"Howard Hughes Medical Institute","ror":"https://ror.org/006w34k90","country_code":"US","type":"facility","lineage":["https://openalex.org/I1344073410"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"C M Crews","raw_affiliation_strings":["Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Cambridge MA, USA. craig.crews@yale.edu"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Cambridge MA, USA. craig.crews@yale.edu","institution_ids":["https://openalex.org/I1344073410"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5113509643","display_name":"W S Lane","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1344073410","display_name":"Howard Hughes Medical Institute","ror":"https://ror.org/006w34k90","country_code":"US","type":"facility","lineage":["https://openalex.org/I1344073410"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"W S Lane","raw_affiliation_strings":["Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Cambridge MA, USA. craig.crews@yale.edu"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Cambridge MA, USA. craig.crews@yale.edu","institution_ids":["https://openalex.org/I1344073410"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5035618234","display_name":"Stuart L. Schreiber","orcid":"https://orcid.org/0000-0003-1922-7558","observed_orcids":["https://orcid.org/0000-0003-1922-7558"]},"institutions":[{"id":"https://openalex.org/I1344073410","display_name":"Howard Hughes Medical Institute","ror":"https://ror.org/006w34k90","country_code":"US","type":"facility","lineage":["https://openalex.org/I1344073410"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"S L Schreiber","raw_affiliation_strings":["Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Cambridge MA, USA. craig.crews@yale.edu"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Cambridge MA, USA. craig.crews@yale.edu","institution_ids":["https://openalex.org/I1344073410"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I1344073410"],"apc_list":null,"apc_paid":null,"fwci":1.5305,"has_fulltext":false,"cited_by_count":51,"citation_normalized_percentile":{"value":0.82003471,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":98},"biblio":{"volume":"93","issue":"9","first_page":"4316","last_page":"4319"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10945","display_name":"Lysosomal Storage Disorders Research","score":0.8910999894142151,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10945","display_name":"Lysosomal Storage Disorders Research","score":0.8910999894142151,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology (medical)"},"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/T11308","display_name":"Sphingolipid Metabolism and Signaling","score":0.07029999792575836,"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/T12604","display_name":"Glycogen Storage Diseases and Myoclonus","score":0.003800000064074993,"subfield":{"id":"https://openalex.org/subfields/2745","display_name":"Rheumatology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/didemnin-b","display_name":"didemnin B","score":0.9940000176429749},{"id":"https://openalex.org/keywords/palmitoyl-protein-thioesterase","display_name":"palmitoyl-protein thioesterase","score":0.9559999704360962},{"id":"https://openalex.org/keywords/infantile-neuronal-ceroid-lipofuscinosis","display_name":"infantile neuronal ceroid lipofuscinosis","score":0.984000027179718},{"id":"https://openalex.org/keywords/protein-protein-binding","display_name":"protein-protein binding","score":0.7089999914169312},{"id":"https://openalex.org/keywords/marine-natural-products","display_name":"marine natural products","score":0.8669999837875366},{"id":"https://openalex.org/keywords/protein-synthesis-inhibition","display_name":"protein synthesis inhibition","score":0.7839999794960022},{"id":"https://openalex.org/keywords/immunosuppression","display_name":"immunosuppression","score":0.6629999876022339},{"id":"https://openalex.org/keywords/cytostasis","display_name":"cytostasis","score":0.6899999976158142},{"id":"https://openalex.org/keywords/cdna-cloning","display_name":"cDNA cloning","score":0.6439999938011169}],"concepts":[{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.5230337381362915},{"id":"https://openalex.org/C2780622759","wikidata":"https://www.wikidata.org/wiki/Q76818446","display_name":"Thioesterase","level":4,"score":0.4678424596786499},{"id":"https://openalex.org/C553089730","wikidata":"https://www.wikidata.org/wiki/Q4914021","display_name":"Binding protein","level":3,"score":0.4125213623046875},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.4105723202228546},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3626268208026886},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.35124629735946655},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.24658417701721191},{"id":"https://openalex.org/C553450214","wikidata":"https://www.wikidata.org/wiki/Q851162","display_name":"Biosynthesis","level":3,"score":0.140257328748703},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.07957983016967773}],"mesh":[{"descriptor_ui":"D000595","descriptor_name":"Amino Acid Sequence","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001483","descriptor_name":"Base Sequence","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001921","descriptor_name":"Brain","qualifier_ui":"Q000201","qualifier_name":"enzymology","is_major_topic":true},{"descriptor_ui":"D001921","descriptor_name":"Brain","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D002417","descriptor_name":"Cattle","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007223","descriptor_name":"Infant","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008969","descriptor_name":"Molecular Sequence Data","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008970","descriptor_name":"Molecular Weight","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009472","descriptor_name":"Neuronal Ceroid-Lipofuscinoses","qualifier_ui":"Q000201","qualifier_name":"enzymology","is_major_topic":true},{"descriptor_ui":"D010456","descriptor_name":"Peptides, Cyclic","qualifier_ui":"Q000096","qualifier_name":"biosynthesis","is_major_topic":false},{"descriptor_ui":"D010456","descriptor_name":"Peptides, Cyclic","qualifier_ui":"Q000302","qualifier_name":"isolation & purification","is_major_topic":false},{"descriptor_ui":"D010456","descriptor_name":"Peptides, Cyclic","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D011485","descriptor_name":"Protein Binding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013869","descriptor_name":"Thiolester Hydrolases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D013869","descriptor_name":"Thiolester Hydrolases","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D016133","descriptor_name":"Polymerase Chain Reaction","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016384","descriptor_name":"Consensus Sequence","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D017386","descriptor_name":"Sequence Homology, Amino Acid","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D017931","descriptor_name":"DNA Primers","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D019204","descriptor_name":"GTP-Binding Proteins","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D047630","descriptor_name":"Depsipeptides","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D051381","descriptor_name":"Rats","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":4,"locations":[{"id":"doi:10.1073/pnas.93.9.4316","doi":"https://doi.org/10.1073/pnas.93.9.4316","is_oa":false,"landing_page_url":"https://doi.org/10.1073/pnas.93.9.4316","pdf_url":null,"source":{"id":"https://openalex.org/S125754415","display_name":"Proceedings of the National Academy of Sciences","issn_l":"0027-8424","issn":["0027-8424","1091-6490"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-a","doyens","erih-plus","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320052","host_organization_name":"National Academy of Sciences","host_organization_lineage":["https://openalex.org/P4310320052"],"host_organization_lineage_names":["National Academy of Sciences"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Proceedings of the National Academy of Sciences","raw_type":"journal-article"},{"id":"pmh:oai:europepmc.org:82633","doi":null,"is_oa":true,"landing_page_url":"http://europepmc.org/pmc/articles/PMC39533","pdf_url":null,"source":{"id":"https://openalex.org/S4306400806","display_name":"Europe PMC (PubMed Central)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1303153112","host_organization_name":"European Bioinformatics Institute","host_organization_lineage":["https://openalex.org/I1303153112"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"","raw_type":"Text"},{"id":"pmh:oai:pubmedcentral.nih.gov:39533","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/39533","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":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Proc Natl Acad Sci U S A","raw_type":"Text"},{"id":"pmid:8633062","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/8633062","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":"Proceedings of the National Academy of Sciences of the United States of America","raw_type":"Comparative Study"}],"best_oa_location":{"id":"pmh:oai:europepmc.org:82633","doi":null,"is_oa":true,"landing_page_url":"http://europepmc.org/pmc/articles/PMC39533","pdf_url":null,"source":{"id":"https://openalex.org/S4306400806","display_name":"Europe PMC (PubMed Central)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1303153112","host_organization_name":"European Bioinformatics Institute","host_organization_lineage":["https://openalex.org/I1303153112"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"","raw_type":"Text"},"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.8371999859809875}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":40,"referenced_works":["https://openalex.org/W1486529618","https://openalex.org/W1514008151","https://openalex.org/W1522289497","https://openalex.org/W1546743612","https://openalex.org/W1963703094","https://openalex.org/W1964222798","https://openalex.org/W1967279802","https://openalex.org/W1969442037","https://openalex.org/W1970047246","https://openalex.org/W1970940462","https://openalex.org/W1973982976","https://openalex.org/W1976335974","https://openalex.org/W1983964771","https://openalex.org/W1984754431","https://openalex.org/W1986119684","https://openalex.org/W1990311250","https://openalex.org/W2003578567","https://openalex.org/W2018289835","https://openalex.org/W2021602387","https://openalex.org/W2029550815","https://openalex.org/W2034344404","https://openalex.org/W2037521932","https://openalex.org/W2057106513","https://openalex.org/W2058852380","https://openalex.org/W2059432078","https://openalex.org/W2074589612","https://openalex.org/W2075429227","https://openalex.org/W2075470612","https://openalex.org/W2088031049","https://openalex.org/W2095269659","https://openalex.org/W2100837269","https://openalex.org/W2115749431","https://openalex.org/W2124551159","https://openalex.org/W2133760881","https://openalex.org/W2138270253","https://openalex.org/W2168847939","https://openalex.org/W2214434127","https://openalex.org/W2323851966","https://openalex.org/W2414934726","https://openalex.org/W2941324397"],"related_works":["https://openalex.org/W2077467993","https://openalex.org/W1966788303","https://openalex.org/W84265137","https://openalex.org/W4220848594","https://openalex.org/W1587308916","https://openalex.org/W2122666486","https://openalex.org/W2225387417","https://openalex.org/W2085119174","https://openalex.org/W2118274026","https://openalex.org/W1981827017"],"abstract_inverted_index":{"The":[0],"marine":[1],"natural":[2],"product":[3],"didemnin":[4,28,56,76],"B,":[5,77],"currently":[6],"in":[7,31,69,137,140],"clinical":[8],"trials":[9],"as":[10],"an":[11,120],"antitumor":[12],"agent,":[13],"has":[14],"several":[15],"potent":[16],"biological":[17],"activities":[18,74],"apparently":[19],"mediated":[20],"by":[21,161],"distinct":[22],"mechanisms.":[23],"Our":[24],"initial":[25],"investigation":[26],"of":[27,34,38,55,75,92,103,133,164],"B":[29,57],"resulted":[30],"the":[32,39,50,66,70,90,104,128],"discovery":[33],"its":[35],"GTP-dependent":[36],"binding":[37],"translation":[40],"elongation":[41],"factor":[42],"EF1":[43],"alpha.":[44],"This":[45],"finding":[46],"is":[47,155],"consistent":[48],"with":[49,115],"protein":[51,97,109,117],"synthesis":[52],"inhibitory":[53],"activity":[54],"observed":[58,78],"at":[59,79],"intermediate":[60],"concentrations.":[61],"To":[62],"begin":[63],"to":[64,146],"dissect":[65],"mechanisms":[67],"involved":[68],"cytostatic":[71],"and":[72,127,167],"immunosuppressive":[73],"low":[80],"concentrations,":[81],"additional":[82],"didemnin-binding":[83,96],"proteins":[84,136],"were":[85],"sought.":[86],"Here":[87],"we":[88],"report":[89],"purification":[91],"a":[93,111,156],"36-kDa":[94],"glycosylated":[95],"from":[98,125],"bovine":[99],"brain":[100,158,165],"lysate.":[101],"Cloning":[102],"human":[105],"cDNA":[106],"encoding":[107],"this":[108],"revealed":[110],"strong":[112],"sequence":[113],"similarity":[114],"palmitoyl":[116],"thioesterase":[118],"(PPT),":[119],"enzyme":[121],"that":[122],"removes":[123],"palmitate":[124],"H-Ras":[126],"G":[129],"alpha":[130],"s":[131],"subunits":[132],"heterotrimeric":[134],"GTP-binding":[135],"vitro.":[138],"Mutations":[139],"PPT":[141],"have":[142],"recently":[143],"been":[144],"shown":[145],"be":[147],"responsible":[148],"for":[149],"infantile":[150],"neuronal":[151],"ceroid":[152],"lipofuscinosis,":[153],"which":[154],"severe":[157],"disorder":[159],"characterized":[160],"progressive":[162],"loss":[163],"function":[166],"early":[168],"death.":[169]},"counts_by_year":[{"year":2024,"cited_by_count":2},{"year":2021,"cited_by_count":1},{"year":2017,"cited_by_count":2},{"year":2016,"cited_by_count":2},{"year":2015,"cited_by_count":4},{"year":2012,"cited_by_count":1}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2016-06-24T00:00:00"}