Delivering a toxic metal to the active site of urease.

Autor:	Nim YS; School of Life Sciences, Centre for Protein Science and Crystallography, State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, China., Fong IYH; Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK., Deme J; Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.; Center for Structural Biology, CCR, NCI, Boyles Street, Frederick, MD 21702, USA., Tsang KL; School of Life Sciences, Centre for Protein Science and Crystallography, State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, China., Caesar J; Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.; Center for Structural Biology, CCR, NCI, Boyles Street, Frederick, MD 21702, USA., Johnson S; Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.; Center for Structural Biology, CCR, NCI, Boyles Street, Frederick, MD 21702, USA., Pang LTH; School of Life Sciences, Centre for Protein Science and Crystallography, State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, China., Yuen NMH; School of Life Sciences, Centre for Protein Science and Crystallography, State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, China., Ng TLC; School of Life Sciences, Centre for Protein Science and Crystallography, State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, China., Choi T; School of Life Sciences, Centre for Protein Science and Crystallography, State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, China., Wong YYH; School of Life Sciences, Centre for Protein Science and Crystallography, State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, China., Lea SM; Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.; Center for Structural Biology, CCR, NCI, Boyles Street, Frederick, MD 21702, USA., Wong KB; School of Life Sciences, Centre for Protein Science and Crystallography, State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, China.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2023 Apr 21; Vol. 9 (16), pp. eadf7790. Date of Electronic Publication: 2023 Apr 21.
DOI:	10.1126/sciadv.adf7790
Abstrakt:	Urease is a nickel (Ni) enzyme that is essential for the colonization of Helicobacter pylori 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 H. pylori UreFD/urease and Klebsiella pneumoniae 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.
Databáze:	MEDLINE
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