prikaz prve stranice dokumenta Uloga dipeptidil-peptidaze III u oksidacijskom stresu
  Download
PDF 5.57 MB
doctoral thesis
Uloga dipeptidil-peptidaze III u oksidacijskom stresu
Zagreb: University of Zagreb, Faculty of Science, 2021. urn:nbn:hr:217:768164
Matić, Sara
University of Zagreb
Faculty of Science
Department of Chemistry

Institutional repository: Repository of the Faculty of Science

Cite this document

Matić, S. (2021). Uloga dipeptidil-peptidaze III u oksidacijskom stresu (Doctoral thesis). Zagreb: University of Zagreb, Faculty of Science. Retrieved from https://urn.nsk.hr/urn:nbn:hr:217:768164

Matić, Sara. "Uloga dipeptidil-peptidaze III u oksidacijskom stresu." Doctoral thesis, University of Zagreb, Faculty of Science, 2021. https://urn.nsk.hr/urn:nbn:hr:217:768164

Matić, Sara. "Uloga dipeptidil-peptidaze III u oksidacijskom stresu." Doctoral thesis, University of Zagreb, Faculty of Science, 2021. https://urn.nsk.hr/urn:nbn:hr:217:768164

Matić, S. (2021). 'Uloga dipeptidil-peptidaze III u oksidacijskom stresu', Doctoral thesis, University of Zagreb, Faculty of Science, accessed 23 December 2024, https://urn.nsk.hr/urn:nbn:hr:217:768164

Matić S. Uloga dipeptidil-peptidaze III u oksidacijskom stresu [Doctoral thesis]. Zagreb: University of Zagreb, Faculty of Science; 2021 [cited 2024 December 23] Available at: https://urn.nsk.hr/urn:nbn:hr:217:768164

S. Matić, "Uloga dipeptidil-peptidaze III u oksidacijskom stresu", Doctoral thesis, University of Zagreb, Faculty of Science, Zagreb, 2021. Available at: https://urn.nsk.hr/urn:nbn:hr:217:768164

Metadata
TitleUloga dipeptidil-peptidaze III u oksidacijskom stresu
Title (english)Role of dipeptidyl peptidase III in oxidative stress response
AuthorSara Matić
MentorSanja Tomić (mentor)
MentorMihaela Matovina (komentor)
Committee memberBranimir Bertoša (predsjednik povjerenstva)
Committee memberJasmina Rokov Plavec (član povjerenstva)
Committee memberFilip Šupljika (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Science
(Department of Chemistry)
Zagreb
Defense date and country2021-09-30, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Chemistry
Universal decimal classification
(UDC)		54 - Chemistry. Crystallography. Mineralogy
Abstract
Razvoj bolesti često je posljedica deregulacije staničnih signalnih putova. Proučavanje interakcija protein-protein kombinacijom eksperimentalnih i računalnih pristupa omogućuje razumijevanje tih staničnih procesa na molekulskoj razini. Signalni put KEAP1 – NRF2, ključan za citoprotektivni odgovor i preživljavanje stanica, često je dereguliran u stanicama raka. KEAP1 je stanični senzor oksidacijskog stresa i represor transkripcijskog faktora NRF2. U uvjetima oksidacijskog stresa dipeptidil-peptidaza III (DPP III) se može kompetitivno vezati na KEAP1 i inducirati oslobađanje NRF2, što potiče antioksidacijski odgovor putem transkripcije citoprotektivnih gena. Korištenjem simulacija molekulske dinamike te izotermne titracijske kalorimetrije i termoforeze proučavan je mehanizam vezanja KEAP1 – DPP III, kako za divlji tip proteina, tako i za mutirane varijante pronađene u stanicama raka. Razumijevanje strukturnih i energetskih učinaka mutacija na brzinu i afinitet vezanja KEAP1 i DPP III u konačnici pojašnjava na koji način navedene mutacije mogu modificirati odgovor stanica raka na kemoterapiju i preživljavanje oksidacijskog stresa.
Abstract (english)
Disease development is often due to deregulation of cellular signaling pathways. Proteinprotein interactions study using a combination of experimental and computational approaches allows understanding of these cellular processes at the molecular level. The KEAP1 – NRF2 signaling pathway, crucial for cytoprotective response and cell survival, is often deregulated in cancer cells. KEAP1 is a cellular oxidative stress sensor and a repressor of NRF2 transcription factor. Under oxidative stress, dipeptidyl peptidase III (DPP III) can competitively bind to KEAP1, inducing NRF2 release and antioxidative response via transcription of cytoprotective genes. Using molecular dynamics simulations, isothermal titration calorimetry and microscale thermophoresis, the mechanism of KEAP1 – DPP III binding was studied for wild-type and mutant variants found in cancer cells. Knowledge of the structural and energetic effects that mutations have on the binding rate and the affinity of KEAP1 - DPP III complexation, enables better understanding of their influence on the cancer cell response to chemotherapy.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:217:768164
Promotion2021
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
Extent115 str. ; 30 cm
File originBorn digital
Access conditionsOpen access
Embargo expiration date: 2022-03-30
Terms of useLicence In copyright icon
Created on2021-10-22 13:18:25