Delivering a toxic metal to the active site of urease

被引：4

作者：

Nim, Yap Shing ^{[1
]}

Fong, Ivan Yu Hang ^{[2
]}

Deme, Justin ^{[2
,3
]}

Tsang, Ka Lung ^{[1
]}

Caesar, Joseph ^{[2
,3
]}

Johnson, Steven ^{[2
,3
]}

Pang, Longson Tsz Hin ^{[1
]}

Yuen, Nicholas Man Hon ^{[1
]}

Ng, Tin Long Chris ^{[1
]}

Choi, Tung ^{[1
]}

Wong, Yakie Yat Hei ^{[1
]}

Lea, Susan M. ^{[2
,3
]}

Wong, Kam-Bo ^{[1
]}

机构：

[1] Chinese Univ Hong Kong, Ctr Prot Sci & Crystallog, Sch Life Sci, State Key Lab Agrobiotechnol, Hong Kong, Peoples R China

[2] Univ Oxford, Sir William Dunn Sch Pathol, South Parks Rd, Oxford OX1 3RE, England

[3] NCI, Ctr Struct Biol, CCR, Boyles St, Frederick, MD 21702 USA

来源：

SCIENCE ADVANCES | 2023年 / 9卷 / 16期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

CRYSTAL-STRUCTURE; NICKEL-TRANSFER; UCSF CHIMERA; PROTEIN; UREF; ACTIVATION; COMPLEX; IDENTIFICATION; NI2+;

D O I：

10.1126/sciadv.adf7790

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：10

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