Delivering a toxic metal to the active site of urease.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37083535.
- Also identified by DOI 10.1126/sciadv.adf7790 and PMC identifier 10121161.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Urease is a nickel (Ni) enzyme that is essential for the colonization of <i>Helicobacter pylori</i> in the human stomach. To solve the problem of delivering the toxic Ni ion to the active site without diffusing into the cytoplasm, cells have evolved metal carrier proteins, or metallochaperones, to deliver the toxic ions to specific protein complexes. Ni delivery requires urease to form an activation complex with the urease accessory proteins UreFD and UreG. Here, we determined the cryo-electron microscopy structures of <i>H. pylori</i> UreFD/urease and <i>Klebsiella pneumoniae</i> UreD/urease complexes at 2.3- and 2.7-angstrom resolutions, respectively. Combining structural, mutagenesis, and biochemical studies, we show that the formation of the activation complex opens a 100-angstrom-long tunnel, where the Ni ion is delivered through UreFD to the active site of urease.
Medical subject headings
- Urease
- Helicobacter pylori