{"id":"https://openalex.org/W1500523379","doi":"https://doi.org/10.1016/s0021-9258(18)67155-8","title":"Evidence for the existence of covalent nucleotide-thymidylate synthase complexes, identification of site of attachment, and enhancement by folates.","display_name":"Evidence for the existence of covalent nucleotide-thymidylate synthase complexes, identification of site of attachment, and enhancement by folates.","publication_year":1986,"publication_date":"1986-09-01","ids":{"openalex":"https://openalex.org/W1500523379","doi":"https://doi.org/10.1016/s0021-9258(18)67155-8","mag":"1500523379","pmid":"https://pubmed.ncbi.nlm.nih.gov/3745210"},"language":"en","primary_location":{"id":"doi:10.1016/s0021-9258(18)67155-8","doi":"https://doi.org/10.1016/s0021-9258(18)67155-8","is_oa":true,"landing_page_url":"https://doi.org/10.1016/s0021-9258(18)67155-8","pdf_url":null,"source":{"id":"https://openalex.org/S140251998","display_name":"Journal of Biological Chemistry","issn_l":"0021-9258","issn":["0021-9258","1067-8816","1083-351X"],"is_oa":false,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-100","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Biological Chemistry","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"hybrid","oa_url":"https://doi.org/10.1016/s0021-9258(18)67155-8","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5112826232","display_name":"M. Moore","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I155781252","display_name":"University of South Carolina","ror":"https://ror.org/02b6qw903","country_code":"US","type":"education","lineage":["https://openalex.org/I155781252"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"M A Moore","raw_affiliation_strings":["From the Department of Chemistry, University of South Carolina, Columbia, South Carolina 29208"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"From the Department of Chemistry, University of South Carolina, Columbia, South Carolina 29208","institution_ids":["https://openalex.org/I155781252"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5026458894","display_name":"Faizy Ahmed","orcid":"https://orcid.org/0000-0002-8686-3266","observed_orcids":["https://orcid.org/0000-0002-8686-3266"]},"institutions":[{"id":"https://openalex.org/I155781252","display_name":"University of South Carolina","ror":"https://ror.org/02b6qw903","country_code":"US","type":"education","lineage":["https://openalex.org/I155781252"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"F Ahmed","raw_affiliation_strings":["From the Department of Chemistry, University of South Carolina, Columbia, South Carolina 29208"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"From the Department of Chemistry, University of South Carolina, Columbia, South Carolina 29208","institution_ids":["https://openalex.org/I155781252"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5000954339","display_name":"R. Bruce Dunlap","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I155781252","display_name":"University of South Carolina","ror":"https://ror.org/02b6qw903","country_code":"US","type":"education","lineage":["https://openalex.org/I155781252"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"R B Dunlap","raw_affiliation_strings":["From the Department of Chemistry, University of South Carolina, Columbia, South Carolina 29208"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"From the Department of Chemistry, University of South Carolina, Columbia, South Carolina 29208","institution_ids":["https://openalex.org/I155781252"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I155781252"],"apc_list":{"value":3430,"currency":"USD","value_usd":3430},"apc_paid":{"value":3430,"currency":"USD","value_usd":3430},"fwci":1.4394,"has_fulltext":false,"cited_by_count":30,"citation_normalized_percentile":{"value":0.81168104,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":94},"biblio":{"volume":"261","issue":"27","first_page":"12745","last_page":"12749"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12827","display_name":"Biochemical and Molecular Research","score":0.9419000148773193,"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/T12827","display_name":"Biochemical and Molecular Research","score":0.9419000148773193,"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/T10499","display_name":"Folate and B Vitamins Research","score":0.027899999171495438,"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"}},{"id":"https://openalex.org/T12191","display_name":"Chemical Reaction Mechanisms","score":0.005900000222027302,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/thymidylate-synthase","display_name":"thymidylate synthase","score":0.9990000128746033},{"id":"https://openalex.org/keywords/dump","display_name":"dUMP","score":0.7670000195503235},{"id":"https://openalex.org/keywords/dtmp","display_name":"dTMP","score":0.9950000047683716},{"id":"https://openalex.org/keywords/folic-acid","display_name":"folic acid","score":0.722000002861023},{"id":"https://openalex.org/keywords/tetrahydrofolate","display_name":"tetrahydrofolate","score":0.9890000224113464},{"id":"https://openalex.org/keywords/dihydrofolate","display_name":"dihydrofolate","score":0.9409999847412109},{"id":"https://openalex.org/keywords/active-site-cysteine","display_name":"active site cysteine","score":0.7860000133514404},{"id":"https://openalex.org/keywords/enzyme-mechanism","display_name":"enzyme mechanism","score":0.6480000019073486}],"concepts":[{"id":"https://openalex.org/C87933860","wikidata":"https://www.wikidata.org/wiki/Q898506","display_name":"Edman degradation","level":4,"score":0.830954909324646},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.7125959396362305},{"id":"https://openalex.org/C180577832","wikidata":"https://www.wikidata.org/wiki/Q127920","display_name":"Covalent bond","level":2,"score":0.6966758370399475},{"id":"https://openalex.org/C41183919","wikidata":"https://www.wikidata.org/wiki/Q423026","display_name":"Active site","level":3,"score":0.6322360038757324},{"id":"https://openalex.org/C2779281246","wikidata":"https://www.wikidata.org/wiki/Q172847","display_name":"Peptide","level":2,"score":0.5896900296211243},{"id":"https://openalex.org/C2777332483","wikidata":"https://www.wikidata.org/wiki/Q410116","display_name":"Trichloroacetic acid","level":2,"score":0.5395805835723877},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.49469301104545593},{"id":"https://openalex.org/C512185932","wikidata":"https://www.wikidata.org/wiki/Q28745","display_name":"Nucleotide","level":3,"score":0.4771147072315216},{"id":"https://openalex.org/C2781338088","wikidata":"https://www.wikidata.org/wiki/Q903495","display_name":"Residue (chemistry)","level":2,"score":0.46402791142463684},{"id":"https://openalex.org/C167625842","wikidata":"https://www.wikidata.org/wiki/Q899763","display_name":"Peptide sequence","level":3,"score":0.4549143314361572},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.454515665769577},{"id":"https://openalex.org/C123321153","wikidata":"https://www.wikidata.org/wiki/Q22676802","display_name":"Thymidylate synthase","level":4,"score":0.45217469334602356},{"id":"https://openalex.org/C515207424","wikidata":"https://www.wikidata.org/wiki/Q8066","display_name":"Amino acid","level":2,"score":0.4208138883113861},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.3996102809906006},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.12628057599067688},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.11910763382911682},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0},{"id":"https://openalex.org/C2780456651","wikidata":"https://www.wikidata.org/wiki/Q238512","display_name":"Fluorouracil","level":3,"score":0.0},{"id":"https://openalex.org/C2776694085","wikidata":"https://www.wikidata.org/wiki/Q974135","display_name":"Chemotherapy","level":2,"score":0.0},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D003856","descriptor_name":"Deoxyuracil Nucleotides","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D005468","descriptor_name":"Fluorodeoxyuridylate","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D005492","descriptor_name":"Folic Acid","qualifier_ui":"Q000031","qualifier_name":"analogs & derivatives","is_major_topic":false},{"descriptor_ui":"D005492","descriptor_name":"Folic Acid","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D013763","descriptor_name":"Tetrahydrofolates","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D013938","descriptor_name":"Thymidine Monophosphate","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D013940","descriptor_name":"Thymidylate Synthase","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true}],"locations_count":2,"locations":[{"id":"doi:10.1016/s0021-9258(18)67155-8","doi":"https://doi.org/10.1016/s0021-9258(18)67155-8","is_oa":true,"landing_page_url":"https://doi.org/10.1016/s0021-9258(18)67155-8","pdf_url":null,"source":{"id":"https://openalex.org/S140251998","display_name":"Journal of Biological Chemistry","issn_l":"0021-9258","issn":["0021-9258","1067-8816","1083-351X"],"is_oa":false,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-100","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Biological Chemistry","raw_type":"journal-article"},{"id":"pmid:3745210","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/3745210","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":"The Journal of biological chemistry","raw_type":"Journal Article"}],"best_oa_location":{"id":"doi:10.1016/s0021-9258(18)67155-8","doi":"https://doi.org/10.1016/s0021-9258(18)67155-8","is_oa":true,"landing_page_url":"https://doi.org/10.1016/s0021-9258(18)67155-8","pdf_url":null,"source":{"id":"https://openalex.org/S140251998","display_name":"Journal of Biological Chemistry","issn_l":"0021-9258","issn":["0021-9258","1067-8816","1083-351X"],"is_oa":false,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-100","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Biological Chemistry","raw_type":"journal-article"},"sustainable_development_goals":[],"study_designs":[],"awards":[{"id":"https://openalex.org/G4531782395","display_name":null,"funder_award_id":"CA 15645","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"}],"funders":[{"id":"https://openalex.org/F4320337351","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":22,"referenced_works":["https://openalex.org/W61938030","https://openalex.org/W581386893","https://openalex.org/W1520243862","https://openalex.org/W1522838898","https://openalex.org/W1524857002","https://openalex.org/W1551398481","https://openalex.org/W1634390593","https://openalex.org/W1963779540","https://openalex.org/W1964554681","https://openalex.org/W1968344011","https://openalex.org/W1972801273","https://openalex.org/W1984220084","https://openalex.org/W1984612986","https://openalex.org/W1991616060","https://openalex.org/W1999565390","https://openalex.org/W2024715692","https://openalex.org/W2034346214","https://openalex.org/W2063023375","https://openalex.org/W2080240343","https://openalex.org/W2082973931","https://openalex.org/W2167847781","https://openalex.org/W2443419555"],"related_works":["https://openalex.org/W3023242220","https://openalex.org/W2034346214","https://openalex.org/W1984612986","https://openalex.org/W2030637592","https://openalex.org/W7095348166","https://openalex.org/W2093527961","https://openalex.org/W1971823484","https://openalex.org/W2010038955","https://openalex.org/W1522838898","https://openalex.org/W2088843418"],"abstract_inverted_index":{"The":[0,54,110],"formation":[1],"of":[2,6,42,51,56,72,91,167,186,205,253],"covalent":[3,43,70,88,144,153,250],"binary":[4,89,145,251],"complexes":[5,90,146,252],"thymidylate":[7],"synthase":[8],"and":[9,16,38,75,105,123,161,169,257],"its":[10],"nucleotide":[11,181],"substrate":[12],"dUMP,":[13],"product":[14],"dTMP,":[15],"inhibitor,":[17],"5-fluorodeoxyuridylate":[18],"(FdUMP)":[19],"was":[20,29,62,114,174,234],"investigated":[21],"using":[22],"the":[23,46,49,69,78,83,92,95,124,134,143,152,170,187,213,216,220,227,229,241,249,261],"trichloroacetic":[24,102],"acid":[25,103,129,173],"precipitation":[26,104],"method.":[27],"It":[28],"observed":[30],"that,":[31],"in":[32,48,68,260],"addition":[33],"to":[34,64,77,107,176,236,240],"FdUMP,":[35,160],"both":[36,73],"dUMP":[37,76,256],"dTMP":[39,258],"were":[40,99,131],"capable":[41],"interactions":[44],"with":[45,80,94,179,199,255],"enzyme":[47,79,93,194,254],"absence":[50],"added":[52],"folates.":[53],"presence":[55],"folate,":[57],"dihydrofolate,":[58],"or":[59],"tetrahydrofolate":[60],"(H4folate)":[61],"found":[63,175,235],"produce":[65],"substantial":[66],"enhancements":[67],"binding":[71],"FdUMP":[74],"H4folate":[81],"being":[82],"most":[84],"effective":[85],"agent.":[86],"Further,":[87],"three":[96],"radiolabeled":[97,180],"nucleotides":[98],"isolated":[100,115],"by":[101,116,133],"subjected":[106],"CNBr":[108,112,190],"cleavage.":[109],"active-site":[111],"peptide":[113,140],"reverse":[117],"phase":[118],"high":[119],"performance":[120],"liquid":[121],"chromatography,":[122],"first":[125],"five":[126],"N-terminal":[127],"amino":[128,172],"residues":[130],"sequenced":[132],"dansyl-Edman":[135],"procedure.":[136],"Each":[137],"active":[138,188,230],"site":[139,189,231],"obtained":[141],"from":[142,151,158,193,219],"as":[147,149],"well":[148],"that":[150,215,248],"inhibitory":[154],"ternary":[155],"complex":[156],"formed":[157],"enzyme,":[159],"5,10-methylene-H4folate":[162],"exhibited":[163],"an":[164],"identical":[165],"sequence":[166,184,204],"Ala-Leu-Pro-Pro-(X)-,":[168],"5th":[171],"be":[177,237],"associated":[178],"ligand.":[182],"Dansyl-Edman":[183],"analysis":[185],"peptide,":[191],"derived":[192],"which":[195],"had":[196],"been":[197],"treated":[198],"iodoacetic":[200],"acid,":[201],"gave":[202],"a":[203],"Ala-Leu-Pro-Pro-CmCys":[206],"(where":[207],"CmCys":[208],"is":[209,223],"carboxymethylcysteine),":[210],"thus":[211],"confirming":[212],"fact":[214],"fifth":[217],"residue":[218,233],"N":[221],"terminus":[222],"Cys-198.":[224],"In":[225],"all":[226],"cases,":[228],"Cys-198":[232],"covalently":[238],"linked":[239],"nucleotides.":[242],"These":[243],"results":[244],"provide":[245],"unequivocal":[246],"proof":[247],"predicted":[259],"catalytic":[262],"reaction":[263],"mechanism":[264],"actually":[265],"exist.":[266]},"counts_by_year":[{"year":2025,"cited_by_count":1},{"year":2022,"cited_by_count":1},{"year":2019,"cited_by_count":1}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2016-06-24T00:00:00"}
