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doctoral thesis
Mehanizmi popravka pogreške leucil-tRNA-sintetaze sprječavaju nekanonsku mistranslaciju proteoma bakterije Escherichia coli
Zagreb: University of Zagreb, Faculty of Science, 2015. urn:nbn:hr:217:762578
Cvetešić, Nevena
University of Zagreb
Faculty of Science
Department of Chemistry

Institutional repository: Repository of the Faculty of Science

Cite this document

Cvetešić, N. (2015). Mehanizmi popravka pogreške leucil-tRNA-sintetaze sprječavaju nekanonsku mistranslaciju proteoma bakterije Escherichia coli (Doctoral thesis). Zagreb: University of Zagreb, Faculty of Science. Retrieved from https://urn.nsk.hr/urn:nbn:hr:217:762578

Cvetešić, Nevena. "Mehanizmi popravka pogreške leucil-tRNA-sintetaze sprječavaju nekanonsku mistranslaciju proteoma bakterije Escherichia coli." Doctoral thesis, University of Zagreb, Faculty of Science, 2015. https://urn.nsk.hr/urn:nbn:hr:217:762578

Cvetešić, Nevena. "Mehanizmi popravka pogreške leucil-tRNA-sintetaze sprječavaju nekanonsku mistranslaciju proteoma bakterije Escherichia coli." Doctoral thesis, University of Zagreb, Faculty of Science, 2015. https://urn.nsk.hr/urn:nbn:hr:217:762578

Cvetešić, N. (2015). 'Mehanizmi popravka pogreške leucil-tRNA-sintetaze sprječavaju nekanonsku mistranslaciju proteoma bakterije Escherichia coli', Doctoral thesis, University of Zagreb, Faculty of Science, accessed 25 November 2024, https://urn.nsk.hr/urn:nbn:hr:217:762578

Cvetešić N. Mehanizmi popravka pogreške leucil-tRNA-sintetaze sprječavaju nekanonsku mistranslaciju proteoma bakterije Escherichia coli [Doctoral thesis]. Zagreb: University of Zagreb, Faculty of Science; 2015 [cited 2024 November 25] Available at: https://urn.nsk.hr/urn:nbn:hr:217:762578

N. Cvetešić, "Mehanizmi popravka pogreške leucil-tRNA-sintetaze sprječavaju nekanonsku mistranslaciju proteoma bakterije Escherichia coli", Doctoral thesis, University of Zagreb, Faculty of Science, Zagreb, 2015. Available at: https://urn.nsk.hr/urn:nbn:hr:217:762578

Metadata
TitleMehanizmi popravka pogreške leucil-tRNA-sintetaze sprječavaju nekanonsku mistranslaciju proteoma bakterije Escherichia coli
Title (english)Proofreading activities of leucyl-tRNA synthetase prevent noncanonical mistranslation of the Escherichia coli proteome
AuthorNevena Cvetešić
MentorIta Gruić Sovulj (mentor)
Committee memberBranimir Bertoša (predsjednik povjerenstva)
Committee memberIta Gruić Sovulj (član povjerenstva)
Committee memberGordana Maravić Vlahoviček (član povjerenstva)
MBZ: 237106
GranterUniversity of Zagreb
Faculty of Science
(Department of Chemistry)
Zagreb
Defense date and country2015-03-18, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Chemistry
Universal decimal classification
(UDC)		54 - Chemistry. Crystallography. Mineralogy
Abstract
Sažetak Aminoacil-tRNA-sintetaze (aaRS) su enzimi koji kataliziraju povezivanje aminokiseline i tRNA. Povezivanje isključivo pripadnog para presudno je za točnu biosintezu proteina. AaRS koje nisu dovoljno specifične za pripadnu aminokiselinu imaju složene mehanizme popravka vlastitih pogrešaka. Popravak se može odvijati prije (hidroliza aminoacil-adenilata) ili nakon prijenosa aminokiseline na tRNA (hidroliza misacilirane tRNA). U ovoj disertaciji detaljno su okarakterizirane sintetska i hidrolitičke reakcije leucil-tRNA-sintetaze (LeuRS) iz bakterije E. coli. Pokazano je da LeuRS ne koristi tRNA-ovisan popravak pogreške prije prijenosa i da pogreške uklanja kroz hidrolizu misacilirane tRNA. Izoleucin je u literaturi istaknut kao dobar supstrat LeuRS koji ugrožava točnost dekodiranja leucinskih kodona. Kinetički eksperimenti pokazuju da LeuRS u sintetskoj reakciji učinkovito isključuje izoleucin, zbog čega popravak pogreške nema ulogu u sprječavanju mistranslacije leucinskih kodona izoleucinom. Nedavno je pokazano da se norvalin, neproteinogena aminokiselina, nakuplja u bakterijskoj citoplazmi u uvjetima nedostatka kisika. Rezultati ove disertacije pokazuju da je glavna biološka funkcija hidrolitičkog popravka LeuRS isključivanje norvalina iz genetičkog koda. Kroz ovo istraživanje otkrivena je poveznica popravka pogreške LeuRS i mehanizama prilagodbe bakterija na rast u uvjetima sa smanjenom količinom kisika.
Abstract (english)
Aminoacyl-tRNA synthetases (aaRS) are enzymes that catalyse pairing of amino acids and tRNAs. As coupling of cognate pairs is crucial for accurate protein biosynthesis, aaRSs have developed complex proofreading mechanisms for correction of errors made in amino acid selection. Proofreading may occur before (hydrolysis of aminoacyl-adenylate), or after transfer of amino acid to tRNA (hydrolysis of misacylated tRNA). Synthetic and hydrolytic reactions of leucyl-tRNA synthetase (LeuRS) are characterised in detail within this thesis. The results demonstrate that LeuRS lacks tRNA-dependent pre-transfer editing and relies on robust post-transfer editing to clear aminoacylation errors. Isoleucine is generally thought to be a significant threat for accurate leucylation. However, kinetic experiments demonstrate that LeuRS efficiently excludes isoleucine in the synthetic reaction and that hydrolytic repair does not have a role in isoleucine elimination. A recent study showed that norvaline, a non-proteinogenic amino acid, accumulates in bacterial cytoplasm during oxygen deprivation. It appears that the major biological role of LeuRS editing is exclusion of norvaline from the genetic code. Research within this thesis reveals that LeuRS editing is interconnected with cellular mechanisms that ensure bacterial adaptability to low-oxygen environment.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:217:762578
Study programmeTitle: Doctoral study in chemistry
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija (doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija)
Type of resourceText
Extent161 str. ; 30 cm
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2017-02-07 13:34:47