DC ElementWertSprache
dc.contributor.advisorIgnatova, Zoya-
dc.contributor.authorKazantsev, Andriy-
dc.date.accessioned2021-07-02T12:32:36Z-
dc.date.available2021-07-02T12:32:36Z-
dc.date.issued2020-
dc.identifier.urihttps://ediss.sub.uni-hamburg.de/handle/ediss/9078-
dc.description.abstractAccurate recognition of base pairs in the processes of Central Dogma is the basis of faithful replication and expression of genetic information. Among the possible sources of errors in this processes, G◦U mismatch recognition during codon-anticodon decoding in translation has the highest error rate. This has been linked to the occurrences of rare enol tautomers of nucleobases, which enable formation of the Watson-Crick (WC) geometry of this mismatch from the wobble (wb) geometry formed with canonical keto tautomers. The WC geometry of G◦U was observed in the environment of the closed ribosomal decoding site in equilibrium structural studies. This observation currently lacks a physicochemical explanation as well as a consistent model to reconcile it with the mechanism of decoding. To address this problem, we studied effects of the decoding site on the wobble↔WC tautomerization reaction in G◦U (wb-WC reaction). Using quantum-mechanical/molecular-mechanical umbrella sampling simulations, we found this reaction to be exoergic in the closed state of the decoding site, but endoergic in the open state. We also calculated the dielectric constant of the decoding site and revealed its decrease in the closed state. Together, these results provide an explanation to the structural observations. To reconcile the stabilization of the WC geometry with the mechanism of base pair recognition in codon-anticodon decoding, we developed a new kinetic model of decoding that incorporates the wb-WC reaction parameters in the open and closed states of the decoding site. In this model, the exoergic wb-WC reaction is kinetically restricted by the decoding rates. This model explains the observations of the WC geometry at equilibrium conditions, thereby uniting structural and kinetic data. Moreover, the model reveals constraints imposed by the exoergic wb-WC reaction on the decoding accuracy: equilibration of the reaction counteracts equilibration of the open-closed transition. Our model can be a step towards a general recognition model for flexible substrates. We applied this model, supported by additional computational studies, to provide a putative mechanism of how a specific U modification in anticodon can facilitate decoding of both A- and G-ending codons.en
dc.language.isoende_DE
dc.publisherStaats- und Universitätsbibliothek Hamburg Carl von Ossietzkyde
dc.rightshttp://purl.org/coar/access_right/c_abf2de_DE
dc.subjectQM/MMen
dc.subjectKinetic modelingen
dc.subjectBase pairen
dc.subjectTautomerismen
dc.subjectSubstrate recognitionen
dc.subject.ddc540: Chemiede_DE
dc.titleNucleobase tautomerism in codon-anticodon decodingen
dc.typedoctoralThesisen
dcterms.dateAccepted2021-03-07-
dc.rights.cchttps://creativecommons.org/licenses/by/4.0/de_DE
dc.rights.rshttp://rightsstatements.org/vocab/InC/1.0/-
dc.subject.bcl35.70: Biochemie: Allgemeinesde_DE
dc.subject.gndRibosomde_DE
dc.subject.gndPrototropiede_DE
dc.subject.gndMolekularmechanikde_DE
dc.subject.gndCodonde_DE
dc.subject.gndGenetischer Codede_DE
dc.type.casraiDissertation-
dc.type.dinidoctoralThesis-
dc.type.driverdoctoralThesis-
dc.type.statusinfo:eu-repo/semantics/publishedVersionde_DE
dc.type.thesisdoctoralThesisde_DE
tuhh.type.opusDissertation-
thesis.grantor.departmentChemiede_DE
thesis.grantor.universityOrInstitutionUniversität Hamburgde_DE
dcterms.DCMITypeText-
datacite.relation.IsSupplementedBydoi:10.6084/m9.figshare.c.5178074.v1de_DE
dc.identifier.urnurn:nbn:de:gbv:18-ediss-93525-
item.advisorGNDIgnatova, Zoya-
item.grantfulltextopen-
item.languageiso639-1other-
item.fulltextWith Fulltext-
item.creatorOrcidKazantsev, Andriy-
item.creatorGNDKazantsev, Andriy-
Enthalten in den Sammlungen:Elektronische Dissertationen und Habilitationen
Dateien zu dieser Ressource:
Datei Beschreibung Prüfsumme GrößeFormat  
wbwc_thesis_VERYFINAL.pdfDissertationf3559b09d69883650c6cce18aaabb4dd15.05 MBAdobe PDFÖffnen/Anzeigen
Zur Kurzanzeige

Info

Seitenansichten

268
Letzte Woche
Letzten Monat
geprüft am 28.03.2024

Download(s)

134
Letzte Woche
Letzten Monat
geprüft am 28.03.2024
Werkzeuge

Google ScholarTM

Prüfe