Unraveling the Helicobacter pylori UreG zinc binding site using X-ray absorption spectroscopy (XAS) and structural modeling

J Biol Inorg Chem. 2012 Mar;17(3):353-61. doi: 10.1007/s00775-011-0857-9. Epub 2011 Nov 9.

Abstract

The pathogenicity of Helicobacter pylori depends on the activity of urease for pH modification. Urease activity requires assembly of a dinickel active site that is facilitated in part by GTP hydrolysis by UreG. The proper functioning of Helicobacter pylori UreG (HpUreG) is dependent on Zn(II) binding and dimerization. X-ray absorption spectroscopy and structural modeling were used to elucidate the structure of the Zn(II) site in HpUreG. These studies independently indicated a site at the dimer interface that has trigonal bipyramidal geometry and is composed of two axial cysteines at 2.29(2) Å, two equatorial histidines at 1.99(1) Å, and a solvent-accessible coordination site. The final model for the Zn(II) site structure was determined by refining multiple-scattering extended X-ray absorption fine structure fits using the geometry predicted by homology modeling and ab initio calculations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Binding Sites
  • Computer Simulation
  • Helicobacter pylori / enzymology*
  • Models, Molecular*
  • Urease* / chemistry
  • Urease* / metabolism
  • X-Ray Absorption Spectroscopy
  • Zinc* / chemistry
  • Zinc* / metabolism

Substances

  • Urease
  • Zinc