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将有毒金属递送到脲酶的活性部位。

Delivering a toxic metal to the active site of urease.

机构信息

School of Life Sciences, Centre for Protein Science and Crystallography, State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, China.

Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.

出版信息

Sci Adv. 2023 Apr 21;9(16):eadf7790. doi: 10.1126/sciadv.adf7790.

Abstract

Urease is a nickel (Ni) enzyme that is essential for the colonization of 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 UreFD/urease and 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.

摘要

脲酶是一种镍(Ni)酶,对于在人体胃中定植至关重要。为了解决将有毒的 Ni 离子递送到活性位点而不扩散到细胞质中的问题,细胞已经进化出金属载体蛋白或金属伴侣蛋白,将有毒离子递送到特定的蛋白质复合物。Ni 的递送需要脲酶与脲酶辅助蛋白 UreFD 和 UreG 形成激活复合物。在这里,我们分别以 2.3 和 2.7 埃的分辨率确定了 UreFD/脲酶和 UreD/脲酶复合物的低温电子显微镜结构。通过结构、突变和生化研究的结合,我们表明激活复合物的形成打开了一个 100 埃长的隧道,其中 Ni 离子通过 UreFD 递送到脲酶的活性位点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a73d/10121161/7cc2d2099b1a/sciadv.adf7790-f1.jpg

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