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doctoral thesis
Molekulsko modeliranje bakterijskih dipeptidil-peptidaza III
Zagreb: University of Zagreb, Faculty of Science, 2018. urn:nbn:hr:217:561583
Tomin, Marko
University of Zagreb
Faculty of Science
Department of Chemistry

Institutional repository: Repository of the Faculty of Science

Cite this document

Tomin, M. (2018). Molekulsko modeliranje bakterijskih dipeptidil-peptidaza III (Doctoral thesis). Zagreb: University of Zagreb, Faculty of Science. Retrieved from https://urn.nsk.hr/urn:nbn:hr:217:561583

Tomin, Marko. "Molekulsko modeliranje bakterijskih dipeptidil-peptidaza III." Doctoral thesis, University of Zagreb, Faculty of Science, 2018. https://urn.nsk.hr/urn:nbn:hr:217:561583

Tomin, Marko. "Molekulsko modeliranje bakterijskih dipeptidil-peptidaza III." Doctoral thesis, University of Zagreb, Faculty of Science, 2018. https://urn.nsk.hr/urn:nbn:hr:217:561583

Tomin, M. (2018). 'Molekulsko modeliranje bakterijskih dipeptidil-peptidaza III', Doctoral thesis, University of Zagreb, Faculty of Science, accessed 04 November 2024, https://urn.nsk.hr/urn:nbn:hr:217:561583

Tomin M. Molekulsko modeliranje bakterijskih dipeptidil-peptidaza III [Doctoral thesis]. Zagreb: University of Zagreb, Faculty of Science; 2018 [cited 2024 November 04] Available at: https://urn.nsk.hr/urn:nbn:hr:217:561583

M. Tomin, "Molekulsko modeliranje bakterijskih dipeptidil-peptidaza III", Doctoral thesis, University of Zagreb, Faculty of Science, Zagreb, 2018. Available at: https://urn.nsk.hr/urn:nbn:hr:217:561583

Metadata
TitleMolekulsko modeliranje bakterijskih dipeptidil-peptidaza III
Title (english)Molecular modellling of bacterial dipeptidyl-peptidases III
AuthorMarko Tomin
MentorSanja Tomić (mentor)
Committee memberBranimir Bertoša (predsjednik povjerenstva)
Committee memberZlatko Mihalić (član povjerenstva)
Committee memberMarija Abramić (član povjerenstva)
Committee memberDavid Matthew Smith (član povjerenstva)
MBZ: 260506
GranterUniversity of Zagreb
Faculty of Science
(Department of Chemistry)
Zagreb
Defense date and country2018-05-24, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Chemistry
Universal decimal classification
(UDC)		54 - Chemistry. Crystallography. Mineralogy
Abstract
Dipeptidil-peptidaza III (DPP III) dvodomenski je protein, metalopeptidaza iz porodice M49, koja u aktivnom mjestu sadrži ion cinka te otcjepljuje dipeptide s N-kraja svojih supstrata. Fokus ove doktorske disertacije bilo je proučavanje strukture i dinamike dviju bakterijskih DPP III: iz mezofila Bacteroides thetaiotaomicron i iz termofila Caldithrix abyssi, te njihovih kompleksa sa sintetičkim supstratima i odabranim inhibitorima. Metodama molekulske dinamike izučavane su konformacijske promjene dugog dosega unutar enzima i pritom je ispitana uspješnost nekoliko polja sila u reproduciranju eksperimentalnih struktura i očekivanih gibanja. Usporedbom strukture i dinamike proteina iz termofilnog i mezofilnog mikroorganizma pružen je uvid u strukturnu osnovu za termalnu stabilnost DPP III iz Caldithrix abyssi. Određeni su biološki relevantni načini vezanja supstrata, odnosno inhibitora, što je omogućilo povezivanje supstratne specifičnosti i aktivnosti pojedinih ortologa sa strukturnim karakteristikama kompleksa i fleksibilnosti enzima. Dobiveni rezultati korišteni su za izradu modelnog sustava DPP III iz Bacteroides thetaiotaomicron koji je podvrgnut kvantno-mehaničkim računima te je predložen mehanizam hidrolize peptidne veze kataliziran od strane navedene peptidaze.
Abstract (english)
Dipeptidyl peptidase III (DPP III) is a two-domain protein, a metallopeptidase from the M49 family which contains a zinc ion within its active site and cleaves dipeptides from the N-terminus of its substrates. The aim of this thesis was was to study the structure and flexibility of DPP III from the mesophilic bacterium Bacteroides thetaiotaomicron and the thermophile Caldithrix abyssi as well as their complexes with synthetic substrates and selected inhibitors. Several force fields have been tested in order to determine the most suitable one for studying the long-range conformational motions of the enzyme. Comparison of results obtained for a termophile with those of a mesophile revealed the structural reasons for thermal stability of DPP III from Caldithrix abyssi. The biologically relevant binding modes of substrates and inhibitors were identified and correlated with structural characteristics of the respective complexes, as well as with the enzyme flexibility. These results were used to build a model system of the Bacteroides thetaiomicron DPP III which was used in a quantum mechanics study in order to propose the reaction mechanism of the peptide bond hydrolysis.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:217:561583
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
Extent124 str. ; 30 cm
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2018-06-05 11:12:12