Heidi Hu/Sandbox 2: Difference between revisions

Accessory proteins HypABCDEF and UreIEFGH facilitate in the maturation of [NiFe]-[http://en.wikipedia.org/wiki/Hydrogenase ''H₂ase''] and [http://en.wikipedia.org/wiki/Urease ''urease''] respectively<ref>PMID:9252185</ref>.  HypA is a nickel metallochaperone normally associated with the maturation of [NiFe]-[http://en.wikipedia.org/wiki/Hydrogenase ''H₂ase'']<ref name="NiTraff">PMID:22970729</ref>.  In H. pylori, however, it is also require for the full activy of urease, despite the presence of the urease-specific Ni-chaperone, UreE<ref>PMID:</ref>.  

The [http://en.wikipedia.org/wiki/Helicobacter_pylori ''H. pylori'']HypA (''Hp''HypA) is a 13.2kDa Ni-chaperone with both a nickel binding site and and structural zinc site.  Zn(II) is coordinated by two CXXC motif each with a flanking histidine, whereas the Ni(II) is known to bind to the N-terminus MHE motif<ref name="bob">PMID:20662514</ref>.  The ''Hp''HypA protein has also been characterized as a monomer or a homodimer.  The N-terminal modified monomeric structure has been solved by NMR (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=2KDX 2KDX])<ref>PMID:</ref>.  The monomeric structure shows an alpha/beta lobe containing the N- and C-termini well separated from the zinc binding lobe (Fig. 1).  The homodimeric ''Hp''HypA has been characterized by NMR to have the similar overall structure with discrepancies to the metal binding sites<ref name="bob"/>.  The metal sites in ''Hp''HypA have been characterized by [http://en.wikipedia.org/wiki/X-ray_absorption_spectroscopy ''X-ray absorption spectroscopy''] (XAS) at pH 6.3 and 7.2 similating the internal pH of H. pylori under acid shock or at neutral pH conditions<ref name="bob"/>.  Whereas the Ni(II) site is 6-coordinate N/O under both pH conditions, the Zn(II) coordination changes from Cys₄ at neutral pH to Cys₂His₂ at acidic pH with nickel-bound<ref name="bob"/> (Fig. 2).  Changes in the coordination of structural Zinc site in response to pH has been hypothesized to be linked to altered HypA structures and protein interaction partners<ref name="bob"/>.

The crystal structure of monomeric (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=3A43 3A43]) and homodimeric (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=3A44 3A44]) HypA from [http://en.wikipedia.org/wiki/Thermococcus_kodakarensis ''Thermococcus kodakarensis''] has been solved<ref>PMID:</ref>.  The HypA homodimer from [http://en.wikipedia.org/wiki/Thermococcus_kodakarensis ''T. kodakarensis''] shows a switch dimer, where one beta strand of each alpha/beta lobe comes from the opposite subunit.  Additionally, each Zn(II) site is coordinated by CXXC motifs from a different subunit. These observations were consistent with the [http://en.wikipedia.org/wiki/Helicobacter_pylori ''H. pylori''] homodimeric HypA NMR data<ref name="bob"/>.

[[Image:HypA-pH-Ni-Change.png|150 px|thumb|Fig. 2: Diagram of Ni- and pH-dependent structural changes to Zn(II) site of ''Hp''HypA (adapted figure<ref name="bob"/>)]]