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.
Interplay of nickel and zinc in metal ion trafficking related to urease / S. Ciurli; B. Zambelli; M. Bellucci; F. Musiani. - ELETTRONICO. - 237:(2009), pp. INOR 611-INOR 611. (Intervento presentato al convegno The 237th ACS National Meeting tenutosi a Salt Lake City, UT, USA nel 22-26 Marzo 2009).
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.
