Crystal Structure of Klebsiella aerogenes UreE, a Nickel-binding Metallochaperone for Urease Activation

Hyun Kyu Song, Scott B. Mulrooney, Robert Huber, Robert P. Hausinger

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

UreE is proposed to be a metallochaperone that delivers nickel ions to urease during activation of this bacterial virulence factor. Wild-type Klebsiella aerogenes UreE binds approximately six nickel ions per homodimer, whereas H144*UreE (a functional C-terminal truncated variant) was previously reported to bind two. We determined the structure of H144*UreE by multi-wavelength anomalous diffraction and refined it to 1.5 Å resolution. The present structure reveals an Hsp40-like peptide-binding domain, an Atx1-like metal-binding domain, and a flexible C terminus. Three metal-binding sites per dimer, defined by structural analysis of Cu-H144*UreE, are on the opposite face of the Atx1-like domain than observed in the copper metallochaperone. One metal bridges the two subunits via the pair of His-96 residues, whereas the other two sites involve metal coordination by His-110 and His-112 within each subunit. In contrast to the copper metallochaperone mechanism involving thiol ligand exchanges between structurally similar chaperones and target proteins, we propose that the Hsp40-like module interacts with urease apoprotein and/or other urease accessory proteins, while the Atx1-like domain delivers histidyl-bound nickel to the urease active site.

Original languageEnglish
Pages (from-to)49359-49364
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number52
DOIs
Publication statusPublished - 2001 Dec 28
Externally publishedYes

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Metallochaperones
Enterobacter aerogenes
Urease
Nickel
Crystal structure
Metals
Chemical activation
Copper
Ions
Apoproteins
Accessories
Virulence Factors
Sulfhydryl Compounds
Structural analysis
Dimers
Catalytic Domain
Proteins
Diffraction
Binding Sites
Ligands

ASJC Scopus subject areas

  • Biochemistry

Cite this

Crystal Structure of Klebsiella aerogenes UreE, a Nickel-binding Metallochaperone for Urease Activation. / Song, Hyun Kyu; Mulrooney, Scott B.; Huber, Robert; Hausinger, Robert P.

In: Journal of Biological Chemistry, Vol. 276, No. 52, 28.12.2001, p. 49359-49364.

Research output: Contribution to journalArticle

Song, Hyun Kyu ; Mulrooney, Scott B. ; Huber, Robert ; Hausinger, Robert P. / Crystal Structure of Klebsiella aerogenes UreE, a Nickel-binding Metallochaperone for Urease Activation. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 52. pp. 49359-49364.
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