Naslov
Structural investigations of purine nucleoside phosphorylase from Helicobacter pylori II

Autori
Luić, Marija ; Gucunski, Karolina ; Leščić Ašler, Ivana ; Štefanić, Zoran

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
29th European Crystallographic Meeting Book of Abstracts / - Zagreb, 2015, 204-204

Skup
29th European Crystallographic Meeting

Mjesto i datum
Rovinj, Hrvatska, 23.08.2015. - 28.08.2015

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
purine nucleoside phosphorylase ; Helicobacter pylori 26695

Sažetak
Helicobacter pylori is a well-known human pathogen involved in the development of many diseases. Due to the ever-growing infection rate and increase of H. pylori antibiotic resistance, it is of utmost importance to find a new way to attack and eradicate H. pylori . The purine metabolism in H. pylori is solely dependent on the salvage pathway and one of the key enzymes in this pathway is purine nucleoside phosphorylase (PNP). Therefore, PNP could be a promising drug target for inhibiting H. pylori growth. Like most bacterial PNPs, H. pylori PNP is a homohexameric protein that can be regarded as a trimer of dimers. The active site conformation of each monomer can be either open or closed (Koellner et al., 2002). In accordance with our hypothesis, substrate binding takes place in open, and catalytic action occurs in the closed conformation. In the crystal structures of the very similar E. coli PNP complexed with its ligands we have found the following distributions of the closed and open active sites: 3 open + 3 closed (Koellner et al., 2002), 4 open + 2 closed sites (Mikleušević et al., 2011). In the frame of this meeting in the presentation "Structural investigations of purine nucleoside phosphorylase from Helicobacter pylori", two crystal structures of the PNP from the H. pylori clinical isolate in complex with ligands will be described. To our surprise, in both crystal structures 5 open + 1 closed conformations were found. To the best of our knowledge, this is first such case among homohexameric PNP enzymes. Very recently, we have obtained also first crystals of the PNP from a referent strain of this bacterium, Helicobacter pylori 26695 in complex with ligands and data collection as well as crystal structure determination is under way. It is important to stress out that in the clinical isolate very important catalytic amino acid Asp204 is mutated in Asn, which, very likely, has implications to the catalytic mechanism. Differences in the active site conformations between PNP enzymes from two different H. pylori strains will be discussed, as well as possible implications on the PNP mechanism of action.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA