Artykuł w czasopiśmie
Brak miniatury
Licencja
ClosedAccessDostęp zamknięty
 

Structure and dynamics of Helicobacter pylori nickel-chaperone HypA: an integrated approach using NMR spectroscopy, functional assays and computational tools.

Uproszczony widok
dc.abstract.enHelicobacter pylori HypA (HpHypA) is a metallochaperone necessary for maturation of [Ni,Fe]-hydrogenase and urease, the enzymes required for colonization and survival of H. pylori in the gastric mucosa. HpHypA contains a structural Zn(II) site and a unique Ni(II) binding site at the N-terminus. X-ray absorption spectra suggested that the Zn(II) coordination depends on pH and on the presence of Ni(II). This study was performed to investigate the structural properties of HpHypA as a function of pH and Ni(II) binding, using NMR spectroscopy combined with DFT and molecular dynamics calculations. The solution structure of apo,Zn-HpHypA, containing Zn(II) but devoid of Ni(II), was determined using 2D, 3D and 4D NMR spectroscopy. The structure suggests that a Ni-binding and a Zn-binding domain, joined through a short linker, could undergo mutual reorientation. This flexibility has no physiological effect on acid viability or urease maturation in H. pylori. Atomistic molecular dynamics simulations suggest that Ni(II) binding is important for the conformational stability of the N-terminal helix. NMR chemical shift perturbation analysis indicates that no structural changes occur in the Zn-binding domain upon addition of Ni(II) in the pH 6.3–7.2 range. The structure of the Ni(II) binding site was probed using 1H NMR spectroscopy experiments tailored to reveal hyperfine-shifted signals around the paramagnetic metal ion. On this basis, two possible models were derived using quantum-mechanical DFT calculations. The results provide a comprehensive picture of the Ni(II) mode to HpHypA, important to rationalize, at the molecular level, the functional interactions of this chaperone with its protein partners.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorMerrell, Scott D
dc.contributor.authorHeidi, Hu
dc.contributor.authorCiurli, Stefano
dc.contributor.authorMaroney, Michael
dc.contributor.authorKoźmiński, Wiktor
dc.contributor.authorJohnson, Ryan C
dc.contributor.authorBardiaux, Benjamin
dc.contributor.authorSpronk, Chris AEM
dc.contributor.authorMusiani, Francesco
dc.contributor.authorZambelli, Barbara
dc.contributor.authorŻerko, Szymon
dc.contributor.authorBasak, Priyanka
dc.contributor.authorPiccioli, Mario
dc.contributor.authorBlum, Faith C
dc.contributor.authorGórka, Michał
dc.date.accessioned2024-01-26T08:21:54Z
dc.date.available2024-01-26T08:21:54Z
dc.date.issued2018
dc.description.financeNie dotyczy
dc.description.number8
dc.description.volume23
dc.identifier.doi10.1007/S00775-018-1616-Y
dc.identifier.issn0949-8257
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/120914
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofJournal of Biological Inorganic Chemistry
dc.relation.pages1309 - 1330
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.subject.enMetallochaperones
dc.subject.enMetal transport
dc.subject.enMolecular dynamics
dc.subject.enNuclear magnetic resonance
dc.subject.enComputational chemistry
dc.subject.enNickel
dc.titleStructure and dynamics of Helicobacter pylori nickel-chaperone HypA: an integrated approach using NMR spectroscopy, functional assays and computational tools.
dc.typeJournalArticle
dspace.entity.typePublication