5XKT

Klebsiella pneumoniae UreG in complex with GMPPNP and nickel

Summary for 5XKT

• Entry DOI: 10.2210/pdb5xkt/pdb
• Descriptor: Urease accessory protein UreG, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, NICKEL (II) ION, ... (4 entities in total)
• Functional Keywords: simibi class gtpase, hydrolase
• Biological source: Klebsiella pneumoniae subsp. rhinoscleromatis SB3432
• Cellular location: Cytoplasm : R4YE37
• Total number of polymer chains: 2
• Total formula weight: 44021.24

Authors

Fong, Y.H.,Yuen, M.H.,Nim, Y.S.,Lau, P.H.,Wong, K.B. (deposition date: 2017-05-09, release date: 2017-12-13, Last modification date: 2023-11-22)

Primary citation

Yuen, M.H.,Fong, Y.H.,Nim, Y.S.,Lau, P.H.,Wong, K.B.
Structural insights into how GTP-dependent conformational changes in a metallochaperone UreG facilitate urease maturation.
Proc. Natl. Acad. Sci. U.S.A., 114:E10890-E10898, 2017

PubMed Abstract: The ability of metallochaperones to allosterically regulate the binding/release of metal ions and to switch protein-binding partners along the metal delivery pathway is essential to the metallation of the metalloenzymes. Urease, catalyzing the hydrolysis of urea into ammonia and carbon dioxide, contains two nickel ions bound by a carbamylated lysine in its active site. Delivery of nickel ions for urease maturation is dependent on GTP hydrolysis and is assisted by four urease accessory proteins UreE, UreF, UreG, and UreH(UreD). Here, we determined the crystal structure of the UreG dimer from in complex with nickel and GMPPNP, a nonhydrolyzable analog of GTP. Comparison with the structure of the GDP-bound UreG (UreG) in the UreGFH complex reveals large conformational changes in the G2 region and residues near the CPH metal-binding motif. Upon GTP binding, the side chains of Cys66 and His68 from each of the UreG protomers rotate toward each other to coordinate a nickel ion in a square-planar geometry. Mutagenesis studies on UreG support the conformational changes induced by GTP binding as essential to dimerization of UreG, GTPase activity, in vitro urease activation, and the switching of UreG from the UreGFH complex to form the UreEG complex with the UreE dimer. The nickel-charged UreE dimer, providing the sole source of nickel, and the UreGFH complex could activate urease in vitro in the presence of GTP. Based on our results, we propose a mechanism of how conformational changes of UreG during the GTP hydrolysis/binding cycle facilitate urease maturation.

PubMed: 29203664
DOI: 10.1073/pnas.1712658114

Experimental method

X-RAY DIFFRACTION (1.8 Å)