Naslov
Conformational changes in adenylosuccinate synthetase from Helicobacter pylori upon ligand binding

Autori
Bubić, Ante ; Narczyk, M. ; Maksymiuk, W. ; Štefanić, Zoran ; Bzowska, A. ; Leščić Ašler, Ivana

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, neobjavljeni rad, znanstveni

Skup
EMBL Conference Bringing molecular structure to life: 50 years of the PDB

Mjesto i datum
Virtual, 20.10.2021. - 22.10.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Helicobacter pylori ; adenylosuccinate synthetase ; X-ray structure ; conformational changes

Sažetak
Human pathogen Helicobacter pylori relies on purine salvage pathway for synthesis of these essential molecules. Adenylosuccinate synthetase (AdSS, EC 6.3.4.4) is one of the enzymes on this pathway and is therefore critical for bacterium’s survival. It catalyzes the synthesis of adenylosuccinate from IMP and aspartate, paired with hydrolysis of one phosphate group from GTP. Our goal is to characterize this enzyme in detail, in order to gain information on its mechanism of action and possibilities for its inhibition. As one of the steps towards this goal, we solved crystal structures of H. pylori AdSS incubated with IMP, hadacidin (inhibitor of AdSS, analogue of aspartate), GTP and Mg2+, as well as of H. pylori AdSS complexed only with IMP. Structures were analyzed and compared between themselves and with unligated structure of Escherichia coli AdSS. This comparison enabled us to identify regions responsible for substrate binding, and conformations these flexible regions adopt with and without bound ligands.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija

POVEZANOST RADA