dc.contributor.author | Urbelienė, Nina | |
dc.contributor.author | Tiškus, Matas | |
dc.contributor.author | Tamulaitienė, Giedrė | |
dc.contributor.author | Gasparavičiūtė, Renata | |
dc.contributor.author | Lapinskaitė, Ringailė | |
dc.contributor.author | Jauniškis, Vykintas | |
dc.contributor.author | Sūdžius, Jurgis | |
dc.contributor.author | Meškienė, Rita | |
dc.contributor.author | Tauraitė, Daiva | |
dc.contributor.author | Skrodenytė, Emilija | |
dc.contributor.author | Urbelis, Gintaras | |
dc.contributor.author | Vaitekūnas, Justas | |
dc.contributor.author | Meškys, Rolandas | |
dc.date.accessioned | 2023-09-18T16:34:47Z | |
dc.date.available | 2023-09-18T16:34:47Z | |
dc.date.issued | 2023 | |
dc.identifier.other | (crossref_id)144788464 | |
dc.identifier.uri | https://etalpykla.vilniustech.lt/handle/123456789/115162 | |
dc.description.abstract | Cytidine deaminases (CDAs) catalyze the hydrolytic deamination of cytidine and 2′-deoxycytidine to uridine and 2′-deoxyuridine. Here, we report that prokaryotic homo-tetrameric CDAs catalyze the nucleophilic substitution at the fourth position of N4-acyl-cytidines, N4-alkyl-cytidines, and N4-alkyloxycarbonyl-cytidines, and S4-alkylth-io-uridines and O4-alkyl-uridines, converting them to uridine and corresponding amide, amine, carbamate, thiol, or alcohol as leaving groups. The x-ray structure of a metagenomic CDA_F14 and the molecular modeling of the CDAs used in this study show a relationship between the bulkiness of a leaving group and the volume of the binding pocket, which is partly determined by the flexible β3α3 loop of CDAs. We propose that CDAs that are active toward a wide range of substrates participate in salvage and/or catabolism of variously modified pyrim-idine nucleosides. This identified promiscuity of CDAs expands the knowledge about the cellular turnover of cytidine derivatives, including the pharmacokinetics of pyrimidine-based prodrugs. | eng |
dc.format | PDF | |
dc.format.extent | p. 1-13 | |
dc.format.medium | tekstas / txt | |
dc.language.iso | eng | |
dc.relation.isreferencedby | Science Citation Index Expanded (Web of Science) | |
dc.rights | Laisvai prieinamas internete | |
dc.source.uri | https://doi.org/10.1126/sciadv.ade4361 | |
dc.source.uri | https://talpykla.elaba.lt/elaba-fedora/objects/elaba:154996727/datastreams/MAIN/content | |
dc.title | Cytidine deaminases catalyze the conversion of N ( S , O ) 4 -substituted pyrimidine nucleosides | |
dc.type | Straipsnis Web of Science DB / Article in Web of Science DB | |
dcterms.license | Creative Commons – Attribution – 4.0 International | |
dcterms.references | 68 | |
dc.type.pubtype | S1 - Straipsnis Web of Science DB / Web of Science DB article | |
dc.contributor.institution | Vilniaus universitetas | |
dc.contributor.institution | Valstybinis mokslinių tyrimų institutas Fizinių ir technologijos mokslų centras Vilniaus universitetas | |
dc.contributor.institution | UAB Biomatter Designs (Biomatter), Vilnius, Lithuania. | |
dc.contributor.institution | Valstybinis mokslinių tyrimų institutas Fizinių ir technologijos mokslų centras | |
dc.contributor.institution | Vilniaus universitetas Vilniaus Gedimino technikos universitetas | |
dc.contributor.faculty | Fundamentinių mokslų fakultetas / Faculty of Fundamental Sciences | |
dc.subject.researchfield | N 003 - Chemija / Chemistry | |
dc.subject.researchfield | N 004 - Biochemija / Biochemistry | |
dc.subject.en | Cytidine deaminases | |
dc.subject.en | CDA | |
dc.subject.en | nucleosides | |
dc.subject.en | pyrimidine nucleosides | |
dcterms.sourcetitle | Science advances | |
dc.description.issue | iss. 5 | |
dc.description.volume | vol. 9 | |
dc.publisher.name | American Association for the Advancement of Science (AAAS) | |
dc.publisher.city | New York | |
dc.identifier.doi | 144788464 | |
dc.identifier.doi | 10.1126/sciadv.ade4361 | |
dc.identifier.elaba | 154996727 | |