prikaz prve stranice dokumenta Priprema, biokemijska i biofizička karakterizacija dviju prolinskih mutiranih varijanti ljudske dipeptidil-peptidaze III
  Download
PDF 1.81 MB
master's thesis
Priprema, biokemijska i biofizička karakterizacija dviju prolinskih mutiranih varijanti ljudske dipeptidil-peptidaze III
Zagreb: University of Zagreb, Faculty of Science, 2022. urn:nbn:hr:217:918165
Miočić-Stošić, Fran
University of Zagreb
Faculty of Science
Department of Chemistry

Institutional repository: Repository of the Faculty of Science

Cite this document

Miočić Stošić, F. (2022). Priprema, biokemijska i biofizička karakterizacija dviju prolinskih mutiranih varijanti ljudske dipeptidil-peptidaze III (Master's thesis). Zagreb: University of Zagreb, Faculty of Science. Retrieved from https://urn.nsk.hr/urn:nbn:hr:217:918165

Miočić Stošić, Fran. "Priprema, biokemijska i biofizička karakterizacija dviju prolinskih mutiranih varijanti ljudske dipeptidil-peptidaze III." Master's thesis, University of Zagreb, Faculty of Science, 2022. https://urn.nsk.hr/urn:nbn:hr:217:918165

Miočić Stošić, Fran. "Priprema, biokemijska i biofizička karakterizacija dviju prolinskih mutiranih varijanti ljudske dipeptidil-peptidaze III." Master's thesis, University of Zagreb, Faculty of Science, 2022. https://urn.nsk.hr/urn:nbn:hr:217:918165

Miočić Stošić, F. (2022). 'Priprema, biokemijska i biofizička karakterizacija dviju prolinskih mutiranih varijanti ljudske dipeptidil-peptidaze III', Master's thesis, University of Zagreb, Faculty of Science, accessed 22 November 2024, https://urn.nsk.hr/urn:nbn:hr:217:918165

Miočić Stošić F. Priprema, biokemijska i biofizička karakterizacija dviju prolinskih mutiranih varijanti ljudske dipeptidil-peptidaze III [Master's thesis]. Zagreb: University of Zagreb, Faculty of Science; 2022 [cited 2024 November 22] Available at: https://urn.nsk.hr/urn:nbn:hr:217:918165

F. Miočić Stošić, "Priprema, biokemijska i biofizička karakterizacija dviju prolinskih mutiranih varijanti ljudske dipeptidil-peptidaze III", Master's thesis, University of Zagreb, Faculty of Science, Zagreb, 2022. Available at: https://urn.nsk.hr/urn:nbn:hr:217:918165

Metadata
TitlePriprema, biokemijska i biofizička karakterizacija dviju prolinskih mutiranih varijanti ljudske dipeptidil-peptidaze III
Title (english)Preparation, biochemical and biophysical characterizaion of two proline mutant variants of human dipeptidyl peptidase III
AuthorFran Miočić-Stošić
MentorMihaela Matovina (mentor)
Committee memberAleksandra Maršavelski (predsjednik povjerenstva)
Committee memberInes Primožič (član povjerenstva)
Committee memberBranimir Bertoša (član povjerenstva)
Committee memberIvan Kodrin (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Science
(Department of Chemistry)
Zagreb
Defense date and country2022-07-15, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Chemistry
Abstract
Dipeptidil-peptidaza III (DPP III) sudjeluje u sustavu razgradnje proteina u stanici, a vjerojatno i u regulaciji krvnog tlaka i boli. DPP III je također uključena u regulaciju signalnog puta Nrf2-Keap1 putem interakcije s proteinom Keap1. Vezanje DPP III na Keap1 onemogućava razgradnju transkripcijskog faktora Nrf2 i povećava njegovu razinu u stanici, što kod tumorskih stanica može povećati otpornost na kemoterapeutike. U bazi za genomiku raka cBioPortal odabrane su mutirane varijante DPP III, P358L i P360S, te je istražen utjecaj mutacija na peptidaznu aktivnost DPP III i interakciju s Keap1. Utvrđeno je da obje mutacije smanjuju konstantu specifičnosti DPP III te da mutacija P358L povećava afinitet DPP III za Keap1. Simulacije molekulske dinamike pokazale su da je petlja preko koje se DPP III veže na Keap1 fleksibilnija u mutantu P358L, što je vjerojatno uzrok većeg afiniteta za Keap1. Daljnjim istraživanjima će se pokušati utvrditi utjecaj mutacije P358L na biološku ulogu DPP III.
Abstract (english)
Dipeptidyl peptidase III (DPP III) participates in the protein turnover, and probably in the regulation of blood pressure and pain. It is also involved in the regulation of Keap1-Nrf2 signaling pathway through interaction with Keap1. Binding of DPP III to Keap1 hinders the degradation of transcription factor Nrf2, and increases its cellular levels, which can cause the resistance of cancer cells to chemotherapeutics. Two mutated variants of DPP III, P358L and P360S were selected from cBioPortal for cancer genomics and the influence of these mutations on DPP III peptidase activity and interaction with Keap1 were investigated. It was found that both mutations lower the specificity constant of DPP III, while P358L mutation increases its affinity for Keap1. Molecular dynamic simulations showed that the loop through which DPP III binds Keap1 is more flexible in P358L mutant, which is a likely cause of the higher affinity for Keap1. Further investigations will try to elucidate the effect of P358L mutation on the biological role of DPP III.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:217:918165
ProjectNumber: IP-2020-02-6743
Title: Interakcija dipeptidil peptidaze III s proteinom SH2 domain-containing protein 3C – moguća veza između odgovora na oksidativni stres i stanične migracije
Title: Dipeptidyl peptidase III interaction with SH2 domain-containing protein 3C – possible link between oxidative stress response and cell migration
Acronym: OxMiLink
Leader: Mihaela Matovina
Jurisdiction: Croatia
Funder: HRZZ
Funding stream: IP
Study programmeTitle: Graduate university studies in chemistry; specializations in: Research programme
Course: Research programme
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
Embargo expiration date: 2023-07-15
Terms of useLicence In copyright icon
Created on2022-09-29 16:43:15