Heidi Hu/Sandbox 2: Difference between revisions

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One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

[[Image:2KDX N to C.png|150 px|thumb|Fig. 1: Structure of monomeric H. pylori HypA (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=2kdx 2KDX]), colored from N- to C-terminus from blue to red.]]

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caption='NMR structure of monomeric H. pylori HypA (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=3A44 3A44])' />

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:19621959</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 [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 <scene name='Heidi_Hu/Sandbox_2/Hphypa/2'>N-terminal modified monomeric structure</scene> (N-terminal tag colored in red) has been solved by NMR (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=2KDX 2KDX])<ref>PMID:19621959</ref>. The monomeric structure shows an <scene name='Heidi_Hu/Sandbox_2/Hphypa_2nd_structure/1'>alpha/beta lobe</scene> containing the N- and C-termini well separated from the <scene name='Heidi_Hu/Sandbox_2/Hphypa_2nd_structure/2'>zinc binding lobe</scene>. 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. 1). 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"/>.

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== Research Interests ==

[[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"/>)]]

[[Image:HypA-pH-Ni-Change.png|180 px|thumb|Fig. 2: Diagram of Ni- and pH-dependent structural changes to Zn(II) site of ''Hp''HypA (adapted figure<ref name="bob"/>)]]

The Ni- and pH-dependent changes in the [http://en.wikipedia.org/wiki/Helicobacter_pylori ''H. pylori''] HypA structural zinc site suggests multiple conformations of this protein. Thus HypA is likely interfacing between the maturation of [NiFe]-[http://en.wikipedia.org/wiki/Hydrogenase ''H2ase''] and/or [http://en.wikipedia.org/wiki/Urease ''urease''] in [http://en.wikipedia.org/wiki/Helicobacter_pylori ''H. pylori''] in a pH-dependent manner, as it is required for the full activation of both of these nickel enzymes. The [http://people.chem.umass.edu/mmaroney/ Maroney Lab] at the University of Massachusetts Amherst is interested in characterizing the conformational changes in HypA and its interaction partners under neutral and acid shock conditions.

Heidi Hu/Sandbox 2: Difference between revisions

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 One of the [[CBI Molecules]] being studied in the  [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].
-[[Image:2KDX N to C.png|150 px|thumb|Fig. 1: Structure of monomeric H. pylori HypA (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=2kdx 2KDX]), colored from N- to C-terminus from blue to red.]]
 <br>
@@ Line 21: / Line 20: @@
 caption='NMR structure of monomeric H. pylori HypA (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=3A44 3A44])' />
 <br>
-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:19621959</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 Cys<sub>4</sub> at neutral pH to Cys<sub>2</sub>His<sub>2</sub> 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 [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 <scene name='Heidi_Hu/Sandbox_2/Hphypa/2'>N-terminal modified monomeric structure</scene> (N-terminal tag colored in red) has been solved by NMR (PDB ID: [http://www.rcsb.org/pdb/explore/explore.do?structureId=2KDX 2KDX])<ref>PMID:19621959</ref>.  The monomeric structure shows an <scene name='Heidi_Hu/Sandbox_2/Hphypa_2nd_structure/1'>alpha/beta lobe</scene> containing the N- and C-termini well separated from the <scene name='Heidi_Hu/Sandbox_2/Hphypa_2nd_structure/2'>zinc binding lobe</scene>.   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 Cys<sub>4</sub> at neutral pH to Cys<sub>2</sub>His<sub>2</sub> at acidic pH with nickel-bound<ref name="bob"/> (Fig. 1).  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"/>.
@@ Line 31: / Line 30: @@
 == Research Interests ==
-[[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"/>)]]
+[[Image:HypA-pH-Ni-Change.png|180 px|thumb|Fig. 2: Diagram of Ni- and pH-dependent structural changes to Zn(II) site of ''Hp''HypA (adapted figure<ref name="bob"/>)]]
 The Ni- and pH-dependent changes in the [http://en.wikipedia.org/wiki/Helicobacter_pylori ''H. pylori''] HypA structural zinc site suggests multiple conformations of this protein.  Thus HypA is likely interfacing between the maturation of [NiFe]-[http://en.wikipedia.org/wiki/Hydrogenase ''H<sub>2</sub>ase''] and/or [http://en.wikipedia.org/wiki/Urease ''urease''] in [http://en.wikipedia.org/wiki/Helicobacter_pylori ''H. pylori''] in a pH-dependent manner, as it is required for the full activation of both of these nickel enzymes. The [http://people.chem.umass.edu/mmaroney/ Maroney Lab] at the University of Massachusetts Amherst is interested in characterizing the conformational changes in HypA and its interaction partners under neutral and acid shock conditions.