Structural insights into how GTP-dependent conformational changes in a metallochaperone UreG facilitate urease maturation

Abstract

Significance Our work provides insights into how cells solve the problem of delivering nickel, a toxic metal, to the active site of a metalloenzyme such as urease. Urease, a nickel-containing enzyme, is a virulence factor for Helicobacter pylori , which infects half of the human population and causes peptic ulcers. Supported by structural and biochemical evidence, we present a paradigm on how a metallochaperone UreG couples GTP hydrolysis/binding to allosterically control the binding/release of nickel ions and to switch protein-binding partners along the metal-delivery pathway so that the nickel ions are passing from one metallochaperone to another, without releasing the “free” toxic metal to the cytoplasm.