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master's thesis
Interdisciplinarno istraživanje mutanata E480Q i T481M ljudske dipeptidil-peptidaze III
Osijek: Josip Juraj Strossmayer University of Osijek, Department of Chemistry, 2021. urn:nbn:hr:182:875563
Martinčić, Monika
Josip Juraj Strossmayer University of Osijek
Department of Chemistry
Department of Analytical, Organic and Applied Chemistry

Institutional repository: Repository of the Department of Chemistry, Osijek

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Martinčić, M. (2021). Interdisciplinarno istraživanje mutanata E480Q i T481M ljudske dipeptidil-peptidaze III (Master's thesis). Osijek: Josip Juraj Strossmayer University of Osijek, Department of Chemistry. Retrieved from https://urn.nsk.hr/urn:nbn:hr:182:875563

Martinčić, Monika. "Interdisciplinarno istraživanje mutanata E480Q i T481M ljudske dipeptidil-peptidaze III." Master's thesis, Josip Juraj Strossmayer University of Osijek, Department of Chemistry, 2021. https://urn.nsk.hr/urn:nbn:hr:182:875563

Martinčić, Monika. "Interdisciplinarno istraživanje mutanata E480Q i T481M ljudske dipeptidil-peptidaze III." Master's thesis, Josip Juraj Strossmayer University of Osijek, Department of Chemistry, 2021. https://urn.nsk.hr/urn:nbn:hr:182:875563

Martinčić, M. (2021). 'Interdisciplinarno istraživanje mutanata E480Q i T481M ljudske dipeptidil-peptidaze III', Master's thesis, Josip Juraj Strossmayer University of Osijek, Department of Chemistry, accessed 27 November 2024, https://urn.nsk.hr/urn:nbn:hr:182:875563

Martinčić M. Interdisciplinarno istraživanje mutanata E480Q i T481M ljudske dipeptidil-peptidaze III [Master's thesis]. Osijek: Josip Juraj Strossmayer University of Osijek, Department of Chemistry; 2021 [cited 2024 November 27] Available at: https://urn.nsk.hr/urn:nbn:hr:182:875563

M. Martinčić, "Interdisciplinarno istraživanje mutanata E480Q i T481M ljudske dipeptidil-peptidaze III", Master's thesis, Josip Juraj Strossmayer University of Osijek, Department of Chemistry, Osijek, 2021. Available at: https://urn.nsk.hr/urn:nbn:hr:182:875563

Metadata
TitleInterdisciplinarno istraživanje mutanata E480Q i T481M ljudske dipeptidil-peptidaze III
Title (english)Interdisciplinary investigation of the human dipeptidyl peptidase III mutants E480Q and T481M
AuthorMonika Martinčić
MentorMartina Šrajer Gajdošik (mentor)
MentorMihaela Matovina (komentor)
MBZ: 254976
Committee memberOlivera Galović (predsjednik povjerenstva)
Committee memberMartina Šrajer Gajdošik (član povjerenstva)
Committee memberMihaela Matovina (član povjerenstva)
MBZ: 254976
GranterJosip Juraj Strossmayer University of Osijek
Department of Chemistry
(Department of Analytical, Organic and Applied Chemistry)
Osijek
Defense date and country2021-07-19, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Chemistry
Applied Chemistry
Abstract
Ljudska dipeptidil–peptidaza III (hDPP III) je metalopeptidaza koja cijepa dipeptide sa N-kraja oligopeptida, te posjeduje ETGE vezni motiv kao i transkripcijski faktor Nrf2. Nrf2 je odgovoran za aktivaciju ekspresije gena vezanih za antioksidativnu obranu stanice. Kada nema oksidativnog stresa, Nrf2 je vezan na protein Keap1 čime se omogućuje njegova ubikvitinacija. Pojavom oksidativnog stresa, Nrf2 se oslobađa iz kompleksa i translocira u jezgru gdje aktivira ekspresiju gena. Kompetativnim vezanjem proteina hDPP III na Keap1 onemogućava se ubikvitinacija Nrf2 čime se povećava njegova akumulacija u stanici. U ovom radu, u bakterijama su proizvedeni i pročišćeni mutanti proteina hDPPP III s mutacijama dviju aminokiselina (T481M i E480Q) čije su genomske sekvence pronađene na cBio portalu za genomiku raka. Biokemijskom karakterizacijom i usporedbom afiniteta vezanja divljeg tipa i mutiranih proteina ispitana je interakcija hDPP III s domenom Kelch proteina Keap1. Na temelju rezultata ovog ispitivanja mogu se donijeti pretpostavke o doprinosu mutacija na otpornost stanica raka na oksidativni stres.
Abstract (english)
Human dipeptidyl-peptidase III (hDPP III) is a metallopeptidase that cleaves dipeptides from the N-terminus of the oligopeptide and has an ETGE binding motif as well as the transcription factor Nrf2. Nrf2 is responsible for activating the expression of genes associated with antioxidant cell defense. When there is no oxidative stress, Nrf2 is bound to Keap1 protein and thus allowing the ubiquitination of Nrf2. With the appearance of oxidative stress, Nrf2 is released from the complex and translocated into the nucleus where it triggers gene expression. Competitive binding of the hDPP III protein to Keap1 prevents the ubiquitination of Nrf2, which in turn increases the accumulation of Nrf2 in the cell. In this thesis, mutants of the hDPPP III protein with mutations of two amino acids (T481M and E480Q), whose genomic sequences were found on the cBio portal for cancer genomics, were produced in bacteria and purified. The interaction of hDPP III with the Keap1 protein was examined by biochemical characterization and by comparison of the binding affinity of wild-type and mutated proteins. Based on the results of this study, assumptions can be made about the contribution of the mutations to cancer cell resistance to oxidative stress.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:182:875563
Study programmeTitle: Graduate University Study of Chemistry; research program; specializations in: Research program
Course: Research program
Study programme type: university
Study level: graduate
Academic / professional title: magistar/magistra kemije (magistar/magistra kemije)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2022-08-03 08:24:27