Naslov
Molecular dynamics study of Helicobacter pylori NikR transcriptional factor

Autori
Bertoša, Branimir ; Magistrato, Alessandra ; Musiani, Francesco ; Ciurli, Stefano ; Carloni, Paolo

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

Skup
The 3rd Adriatic Meeting on Computational Solutions in the Life Sciences

Mjesto i datum
Primošten, Hrvatska, 01.09.2009. - 05.09.2009

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
helicobacter pylori ; NikR ; molecular dynamics

Sažetak
NikR is a nickel-dependent transcriptional factor that regulates the expression of genes coding for proteins involved in the modulation of intracellular concentration of nickel ions (Ni2+) in the pathogen Helicobacter pylori (Hp), and is crucial for its survival in human stomach. To investigate the mechanism through which Ni2+ affects the protein structural and dynamics properties and consequently its affinity towards DNA, different states of the protein (open, closed-trans and closed-cis) were modelled. They differ for the relative orientation of DNA Binding Domains (DBDs) according to the ACT domain (metal binding domain). For each state, different models considering Ni2+ presence in high affinity binding sites were constructed. Each model was subjected to 40 ns long molecular dynamics simulations in explicit water as well as to Poisson-Boltzmann calculations. The ACT domain turned out to rearrange differently depending on the presence or the absence of Ni2+ ions. Contraction of ACT domain during the simulation of the protein fully loaded with Ni2+ is achieved through formation of a hydrogen bond network. Changes of the ACT domain affect rearrangement of DBDs and, consequently, proteins ability to bind DNA. Furthermore, the presence of Ni2+ ions causes an increase of positive potential in the DNA binding region, consistent with the experimental fact that that the presence of the ions increases its affinity for DNA.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA