National Institutes of Health/National Cancer Institute (NIH/NCI)
米国
Wellcome Trust
219477
英国
Medical Research Council (MRC, United Kingdom)
S021264
英国
引用
ジャーナル: Sci Adv / 年: 2023 タイトル: Delivering a toxic metal to the active site of urease. 著者: Yap Shing Nim / Ivan Yu Hang Fong / Justin Deme / Ka Lung Tsang / Joseph Caesar / Steven Johnson / Longson Tsz Hin Pang / Nicholas Man Hon Yuen / Tin Long Chris Ng / Tung Choi / Yakie Yat Hei ...著者: Yap Shing Nim / Ivan Yu Hang Fong / Justin Deme / Ka Lung Tsang / Joseph Caesar / Steven Johnson / Longson Tsz Hin Pang / Nicholas Man Hon Yuen / Tin Long Chris Ng / Tung Choi / Yakie Yat Hei Wong / Susan M Lea / Kam-Bo Wong / 要旨: 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 ...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.