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master's thesis
Mehanizam redukcije HMG-CoA katalizirane ljudskom HMG-CoA reduktazom
Osijek: Josip Juraj Strossmayer University of Osijek, Department of Chemistry, 2018. urn:nbn:hr:182:104606
Mihaljević-Jurič, Paula
Josip Juraj Strossmayer University of Osijek
Department of Chemistry
Department of General, Inorganic and Physical Chemistry and Methodology of Chemistry

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Mihaljević Jurič, P. (2018). Mehanizam redukcije HMG-CoA katalizirane ljudskom HMG-CoA reduktazom (Master's thesis). Retrieved from https://urn.nsk.hr/urn:nbn:hr:182:104606

Mihaljević Jurič, Paula. "Mehanizam redukcije HMG-CoA katalizirane ljudskom HMG-CoA reduktazom." Master's thesis, Josip Juraj Strossmayer University of Osijek, Department of Chemistry, 2018. https://urn.nsk.hr/urn:nbn:hr:182:104606

Mihaljević Jurič, Paula. "Mehanizam redukcije HMG-CoA katalizirane ljudskom HMG-CoA reduktazom." Master's thesis, Josip Juraj Strossmayer University of Osijek, Department of Chemistry, 2018. https://urn.nsk.hr/urn:nbn:hr:182:104606

Mihaljević Jurič, P. (2018). 'Mehanizam redukcije HMG-CoA katalizirane ljudskom HMG-CoA reduktazom', Master's thesis, Josip Juraj Strossmayer University of Osijek, Department of Chemistry, accessed 25 March 2023, https://urn.nsk.hr/urn:nbn:hr:182:104606

Mihaljević Jurič P. Mehanizam redukcije HMG-CoA katalizirane ljudskom HMG-CoA reduktazom [Master's thesis]. Osijek: Josip Juraj Strossmayer University of Osijek, Department of Chemistry; 2018 [cited 2023 March 25] Available at: https://urn.nsk.hr/urn:nbn:hr:182:104606

P. Mihaljević Jurič, "Mehanizam redukcije HMG-CoA katalizirane ljudskom HMG-CoA reduktazom", Master's thesis, Josip Juraj Strossmayer University of Osijek, Department of Chemistry, Osijek, 2018. Available at: https://urn.nsk.hr/urn:nbn:hr:182:104606

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Metadata
TitleMehanizam redukcije HMG-CoA katalizirane ljudskom HMG-CoA reduktazom
Title (english)The Mechanism of Reduction of HMG-CoA Catalyzed by Human HMG-CoA Reductase
AuthorPaula Mihaljević-Jurič
MentorMartina Medvidović-Kosanović (mentor)
Committee memberElvira Kovač-Andrić (predsjednik povjerenstva)
Committee memberMartina Medvidović-Kosanović (član povjerenstva)
Committee memberMirela Samardžić (član povjerenstva)
GranterJosip Juraj Strossmayer University of Osijek
Department of Chemistry
(Department of General, Inorganic and Physical Chemistry and Methodology of Chemistry)
Osijek
Defense date and country2018-07-05, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Chemistry
Physical Chemistry
Abstract
Redukcijski mehanizam HMG-CoA katalizirane ljudskom HMG-CoA reduktazom ispitivan je QM/MM (ONIOM) metodom. Sustav je podijeljen na dva dijela gdje se aktivno mjesto tretiralo kvantnom mehanikom (DFT, B3LYP), a ostatak enzima s klasičnim metodama molekularne mehanike. Istraživana su tri različita modela drugog hidridnog prijelaza mehanizma s različitim protonacijskim stanjima katalitičkih amino kiselinskih ostataka. U aktivnom mjestu nalazio se NADPH kofaktor, mevaldehid substrat te glutamat, lizin, aspartat i histidin (Glu98, Lys639, Asp715 i His405). Metodom molekularne dinamike (MD) dobila se najpovoljnija konformacija početne kristalografske strukture, koja se koristila u svim daljnjim simulacijama. U prvom modelu glutamta i aspartat su bili deprotonirani, lizin je bio protoniran, a histidin dvostruko protoniran, dok je u drugom modelu histidin bio protoniran, a u trećem modelu lizin deprotoniran.
Abstract (english)
Reduction mechanism of HMG-CoA catalysed by human HMG-CoA reductase has been studied with the QM/MM (ONIOM) method. The system has been partitioned in two parts where the active site was treated with quantum mechanics (DFT, B3LYP) and the rest of the enzyme with classical methods of molecular mechanics. The second hydride transfer of the catalytic mechanism have been studied through three different models with different protonation states of the catalytic residues. In the active site NADPH cofactor, mevaldehyde substrate, glutamate, lysine, aspartate and histidine (Glu559, Lys639, Asp715 i His405) were placed. Through molecular dynamics simulations the most favourable conformation of the initial crystallographic structure was obtained and used throughout all the later simulations. In the first model, glutamate and aspartame were deprotonated, lysin was protonated and histidine was doubleprotonated, whereas in the second model, histidine was protonated, and in third model lysine was deprotonated.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:182:104606
Study programmeTitle: Graduate University Study of Chemistry; research direction
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
RepositoryRepository of the Department of Chemistry, Osijek
Created on2018-12-31 09:15:57