The essentiality of Ni2+ for urease activity demands proper intracellular Ni2+ trafficking. The metallo-chaperone UreE delivers Ni2+ into the apo-enzyme in the last step of urease maturation, concomitantly with GTP hydrolysis catalyzed by UreG. This study is focused on UreE and UreG from Helicobacter pylori, a ureolytic bacterium responsible for gastric ulcers and cancer. HpUreG tightly binds 0.5 equivalents of Zn2+ per monomer, whereas it has 20-fold lower affinity for Ni2+. Zn2+ binding (but not Ni2+ binding) causes HpUreG dimerization. The role of conserved protein residues in metal binding was verified by site-directed mutagenesis. HpUreE binds one equivalent of Ni2+ or Zn2+ per dimer, with protein conformation depending on the metal ion. A stable UreE-UreG protein complex, specifically induced by Zn2+ and not by Ni2+, was identified and a viable structure calculated. A possible role for Zn2+ in the Ni2+-dependent urease assembly process mediated by UreE and UreG is envisaged.
S. Ciurli, B. Zambelli, M. Bellucci, F. Musiani (2009). Interplay of nickel and zinc in metal ion trafficking related to urease. SALT LAKE CITY : American Chemical Society.
Interplay of nickel and zinc in metal ion trafficking related to urease
CIURLI, STEFANO LUCIANO;ZAMBELLI, BARBARA;BELLUCCI, MATTEO;MUSIANI, FRANCESCO
2009
Abstract
The essentiality of Ni2+ for urease activity demands proper intracellular Ni2+ trafficking. The metallo-chaperone UreE delivers Ni2+ into the apo-enzyme in the last step of urease maturation, concomitantly with GTP hydrolysis catalyzed by UreG. This study is focused on UreE and UreG from Helicobacter pylori, a ureolytic bacterium responsible for gastric ulcers and cancer. HpUreG tightly binds 0.5 equivalents of Zn2+ per monomer, whereas it has 20-fold lower affinity for Ni2+. Zn2+ binding (but not Ni2+ binding) causes HpUreG dimerization. The role of conserved protein residues in metal binding was verified by site-directed mutagenesis. HpUreE binds one equivalent of Ni2+ or Zn2+ per dimer, with protein conformation depending on the metal ion. A stable UreE-UreG protein complex, specifically induced by Zn2+ and not by Ni2+, was identified and a viable structure calculated. A possible role for Zn2+ in the Ni2+-dependent urease assembly process mediated by UreE and UreG is envisaged.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
