Structure of a Nickel Chaperone, HypA, from Helicobacter pylon Reveals Two Distinct Metal Binding Sites.

Metaltochaperones bind metals and ensure the safe delivery of metals to the targets. They are required for the activation and maturation of nickel-containing enzymes [Ni,Fe]-hydrogenase and urease. Metallochaperone HypA was found to be essential to facilitate nickel delivery to hydrogenase together...

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Publicado en:Journal of the American Chemical Society Vol. 131; no. 29; pp. 10031 - 10041
Autores principales: Xia, Wei, Li, Hongyan, Sze, Kong-Hung, Sun, Hongzhe
Formato: Artículo
Publicado: American Chemical Society 7/29/2009
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Acceso en línea:Ver este registro en EBSCOhost
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        10.1021/ja900543y
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        atl: Structure of a Nickel Chaperone, HypA, from Helicobacter pylon Reveals Two Distinct Metal Binding Sites.
      aug:
        au:
          Xia, Wei
          Li, Hongyan
          Sze, Kong-Hung
          Sun, Hongzhe
        affil: Department of Chemistry and Open Laboratory of Chemical Biology, University of Hong Kong, Pokfulam, Hong Kong, People's Republic of China
      su:
        Molecular chaperones
        Nickel compounds
        Metal bonding
        Binding sites
        Helicobacter pylori
        Zinc compounds
        Nuclear magnetic resonance spectroscopy
        Cysteine proteinases
      sug:
        subj:
          Molecular chaperones
          Nickel compounds
          Metal bonding
          Binding sites
          Helicobacter pylori
          Zinc compounds
          Nuclear magnetic resonance spectroscopy
          Cysteine proteinases
      ab: Metaltochaperones bind metals and ensure the safe delivery of metals to the targets. They are required for the activation and maturation of nickel-containing enzymes [Ni,Fe]-hydrogenase and urease. Metallochaperone HypA was found to be essential to facilitate nickel delivery to hydrogenase together with its partner HypB, although the detailed mechanism is not clear. In this study, we have cloned hypA gene from Helicobacterpylori (strain 26695), overexpressed, and purified the protein. The zinc-bound HypA (Zn-HypA) exists as a monomer in solution, and its solution structure was determined by NMA spectroscopy together with molecular dynamics simulated annealing. Zn-HypA folds into two domains, including a zinc domain and a nickel domain with a mixed α/β structure. The former houses a rigid zinc-binding site possibly with the role of structural stabilization, whereas the latter harbors a nickel-binding site at the N-terminus. Zinc binds to the four conserved cysteines tetrahedrally as evidenced by Cd NMR spectroscopy, and nickel coordinates with four nitrogens of the protein probably in a square-planar geometry. Low coordination number of Ni may allow the metal to be readily transferred to its downstream receptors. Our studies may shed light on how the metallochaperone exerts its functions in intracellular nickel delivery.
      pubtype: Academic Journal
      doctype: Article
      src: R
    language: English
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