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Klebsiella pneumoniae UreG in complex with GMPPNP and nickel
Structural highlights
FunctionR4YE37_KLEPR Facilitates the functional incorporation of the urease nickel metallocenter. This process requires GTP hydrolysis, probably effectuated by UreG.[HAMAP-Rule:MF_01389][SAAS:SAAS00098435] Publication Abstract from PubMedThe 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 Klebsiella pneumoniae in complex with nickel and GMPPNP, a nonhydrolyzable analog of GTP. Comparison with the structure of the GDP-bound Helicobacter pylori UreG (HpUreG) in the UreG2F2H2 complex reveals large conformational changes in the G2 region and residues near the 66CPH68 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 HpUreG 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 UreG2F2H2 complex to form the UreE2G2 complex with the UreE dimer. The nickel-charged UreE dimer, providing the sole source of nickel, and the UreG2F2H2 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. Structural insights into how GTP-dependent conformational changes in a metallochaperone UreG facilitate urease maturation.,Yuen MH, Fong YH, Nim YS, Lau PH, Wong KB Proc Natl Acad Sci U S A. 2017 Dec 19;114(51):E10890-E10898. doi:, 10.1073/pnas.1712658114. Epub 2017 Dec 4. PMID:29203664[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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