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doctoral thesis
Vezanje iona prijelaznih metala u ljudskoj dipeptidil-peptidazi III
Zagreb: University of Zagreb, Faculty of Science, 2024. urn:nbn:hr:217:874265
Matić, Antonia
University of Zagreb
Faculty of Science
Department of Chemistry

Institutional repository: Repository of the Faculty of Science

Cite this document

Matić, A. (2024). Vezanje iona prijelaznih metala u ljudskoj dipeptidil-peptidazi III (Doctoral thesis). Zagreb: University of Zagreb, Faculty of Science. Retrieved from https://urn.nsk.hr/urn:nbn:hr:217:874265

Matić, Antonia. "Vezanje iona prijelaznih metala u ljudskoj dipeptidil-peptidazi III." Doctoral thesis, University of Zagreb, Faculty of Science, 2024. https://urn.nsk.hr/urn:nbn:hr:217:874265

Matić, Antonia. "Vezanje iona prijelaznih metala u ljudskoj dipeptidil-peptidazi III." Doctoral thesis, University of Zagreb, Faculty of Science, 2024. https://urn.nsk.hr/urn:nbn:hr:217:874265

Matić, A. (2024). 'Vezanje iona prijelaznih metala u ljudskoj dipeptidil-peptidazi III', Doctoral thesis, University of Zagreb, Faculty of Science, accessed 13 September 2024, https://urn.nsk.hr/urn:nbn:hr:217:874265

Matić A. Vezanje iona prijelaznih metala u ljudskoj dipeptidil-peptidazi III [Doctoral thesis]. Zagreb: University of Zagreb, Faculty of Science; 2024 [cited 2024 September 13] Available at: https://urn.nsk.hr/urn:nbn:hr:217:874265

A. Matić, "Vezanje iona prijelaznih metala u ljudskoj dipeptidil-peptidazi III", Doctoral thesis, University of Zagreb, Faculty of Science, Zagreb, 2024. Available at: https://urn.nsk.hr/urn:nbn:hr:217:874265

Metadata
TitleVezanje iona prijelaznih metala u ljudskoj dipeptidil-peptidazi III
Title (english)Binding of transition metal ions into human dipeptidyl peptidase III
AuthorAntonia Matić
MentorSanja Tomić (mentor)
Committee memberAleksandra Maršavelski (predsjednik povjerenstva)
Committee memberIvana Leščić Ašler (član povjerenstva)
Committee memberIvo Crnolatac (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Science
(Department of Chemistry)
Zagreb
Defense date and country2024-02-16, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Chemistry
Universal decimal classification
(UDC)		54 - Chemistry. Crystallography. Mineralogy
Abstract
Cilj istraživanja bio je odrediti učinak vezanja različitih dvovalentnih iona metala: Zn2+, Mn2+, Co2+, Cu2+, u različitim koncentracijama, na aktivnost ljudske dipeptidil-peptidaze III (hDPP III), istražiti pretpostavku postojanja inhibitornog veznog mjesta metala i ukoliko je točna, identificirati ga. Istraživanja su provedena kombiniranjem različitih eksperimentalnih i računalnih metoda. Za potrebe eksperimentalnog istraživanja pripremljeni su holoenzimi s ionima Zn2+, Mn2+, Co2+ i Cu2+. U tim uzorcima stehiometrija metal-protein određena je spektrometrijom masa s induktivno spregnutom plazmom (ICP-MS) i izotermalnom titracijskom kalorimetrijom (ITC). Koristeći metodu spektroskopije zaustavljenog protoka, pratilo se smanjenje enzimske aktivnosti hDPP III uzrokovano viškom iona metala. Računalnim metodama, kvantno mehaničkim izračunima i molekulsko dinamičkim simulacijama, određeni su afiniteti različitih kationa metala prema aktivnom mjestu hDPP III, identificirana su inhibitorna vezna mjesta za ione bakra i cinka i određen je mehanizam izmjene metalnih iona vezanih u inhibitorno i katalitičko vezno mjesto.
Abstract (english)
The aim of the study was to determine the binding effect of various divalent ionic metals: Zn2+, Mn2+, Co2+, Cu2+, in different concentrations, on the activity of human dipeptidyl peptidase III (hDPP III), to verify our assumption of the existence of an inhibitory metal binding site and, if correct, to identify this site. The investigations were carried out by combining different experimental and computational methods. For the experimental studies, holoenzymes with Zn2+, Mn2+, Co2+, and Cu2+ ions were prepared. In these samples, the metal-protein stoichiometry was determined by inductively coupled plasma mass spectrometry (ICP-MS) and isothermal titration calorimetry (ITC). Stopped flow spectroscopy was used to monitor the decrease in hDPP-III enzyme activity due to an excess of metal ions. Computational methods, quantum mechanical calculations and molecular dynamics simulations were used to determine the affinities of different metal dications to the active site of hDPP III, to identify the inhibitory binding site for copper and zinc ions and to determine the mechanism of exchange of metal ions bound to the inhibitory and catalytic binding sites.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:217:874265
Promotion2024
ProjectNumber: IP-2018-01-2936
Title: Biološka važnost dipeptidil peptidaze III i njezin utjecaj na zdravlje čovjeka
Acronym: DPP3BioRe
Leader: Sanja Tomić
Jurisdiction: Croatia
Funder: HRZZ
Funding stream: IP
Study programmeTitle: Doctoral study
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica u području prirodnih znanosti (doktor/doktorica u području prirodnih znanosti)
Type of resourceText
Extent115 str. ; 30 cm
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2024-02-29 10:48:58