prikaz prve stranice dokumenta Strukturna istraživanja enzima purinske nukleozidne fosforilaze iz bakterije Helicobacter pylori
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master's thesis
Strukturna istraživanja enzima purinske nukleozidne fosforilaze iz bakterije Helicobacter pylori
Zagreb: University of Zagreb, Faculty of Science, 2017. urn:nbn:hr:217:510076
Papa, Lucija
University of Zagreb
Faculty of Science
Department of Chemistry

Institutional repository: Repository of the Faculty of Science

Cite this document

Papa, L. (2017). Strukturna istraživanja enzima purinske nukleozidne fosforilaze iz bakterije Helicobacter pylori (Master's thesis). Zagreb: University of Zagreb, Faculty of Science. Retrieved from https://urn.nsk.hr/urn:nbn:hr:217:510076

Papa, Lucija. "Strukturna istraživanja enzima purinske nukleozidne fosforilaze iz bakterije Helicobacter pylori." Master's thesis, University of Zagreb, Faculty of Science, 2017. https://urn.nsk.hr/urn:nbn:hr:217:510076

Papa, Lucija. "Strukturna istraživanja enzima purinske nukleozidne fosforilaze iz bakterije Helicobacter pylori." Master's thesis, University of Zagreb, Faculty of Science, 2017. https://urn.nsk.hr/urn:nbn:hr:217:510076

Papa, L. (2017). 'Strukturna istraživanja enzima purinske nukleozidne fosforilaze iz bakterije Helicobacter pylori', Master's thesis, University of Zagreb, Faculty of Science, accessed 14 May 2024, https://urn.nsk.hr/urn:nbn:hr:217:510076

Papa L. Strukturna istraživanja enzima purinske nukleozidne fosforilaze iz bakterije Helicobacter pylori [Master's thesis]. Zagreb: University of Zagreb, Faculty of Science; 2017 [cited 2024 May 14] Available at: https://urn.nsk.hr/urn:nbn:hr:217:510076

L. Papa, "Strukturna istraživanja enzima purinske nukleozidne fosforilaze iz bakterije Helicobacter pylori", Master's thesis, University of Zagreb, Faculty of Science, Zagreb, 2017. Available at: https://urn.nsk.hr/urn:nbn:hr:217:510076

Metadata
TitleStrukturna istraživanja enzima purinske nukleozidne fosforilaze iz bakterije Helicobacter pylori
Title (english)Structural investigation of enzyme purine nucleoside phosphorylase from bacteria Helicobacter pylori
AuthorLucija Papa
MentorMarija Luić (mentor)
Committee memberDubravka Matković-Čalogović (predsjednik povjerenstva)
Committee memberMarija Luić (član povjerenstva)
Committee memberDavor Kovačević (član povjerenstva)
Committee memberMarijana Đaković (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Science
(Department of Chemistry)
Zagreb
Defense date and country2017-02-21, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Chemistry
Abstract
Bakterija Helicobacter pylori, patogen ljudskog probavnog sustava, za biosintezu purinskih nukleozida koristi samo pomodni metabolički put. Smatra se da bi inhibicija ključnih enzima navedenog puta mogla inhibirati rast ove bakterije. Jedan od takvih enzima je purinska nukleozidna fosforilaza (PNP), koja katalizira fosforolitičko cijepanje glikozidne veze u purinskim nukleozidima. Kako bi se što bolje razumjelo vezanje liganada u aktivno mjesto PNP, pripremljeni su kristali binarnih kompleksa PNP s fosfatnim anionom, te s formicinom A - strukturnim analogom purinskog nukleozida adenozina, kao i kristali ternarnog kompleksa koji sadrži oba liganda. Trodimenzijske strukture kompleksa određene su metodom difrakcije rendgenskog zračenja na jediničnom kristalu. Vezanje fosfatnih aniona u aktivna mjesta enzima, koje je mogude samo u uvjetima snižene ionske jakosti, vjerojatno dovodi do konformacijske promjene u podjedinici i zatvaranja aktivnog mjesta. U otvorenim aktivnim mjestima konformacija formicina A razlikuje se od one u zatvorenim aktivnim mjestima. Navedeno je u skladu s trenutno pretpostavljenim katalitičkim mehanizmom za sličan PNP iz bakterije E. coli.
Abstract (english)
Bacterium Helicobacter pylori is a known human digestive system pathogen. For biosynthesis of purine nucleosides it relies exclusively on salvage pathway, therefore, new medicine could be developed by inhibiting salvage pathway's crucial enzymes. Purine nucleoside phosphorylase (PNP), one of those enzymes, catalyzes phosphorolytic cleavage of the glycosidic bond in purine nucleosides. Binary complexes of PNP with phosphate ions (natural substrate) and formycin A (natural substrate's uncleavable structural analogue), and ternary complex of PNP with both of those ligands were prepared and crystallized in order to explore ligand binding into the active sites of the enzyme. Structures of the prepared complexes were determined using single-crystal X-ray crystallography. Closing of the active sites is probably caused by conformational changes driven by phosphate binding, possible only in low ionic strength conditions. Formycin A adopts different conformations in open and closed active sites. Observed effects are in agreement with the currently proposed catalytic mechanism of the similar PNP protein from E. coli.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:217:510076
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: 2018-08-21
Terms of useLicence In copyright icon
Created on2017-03-03 13:25:22