Crystal structures of the UDP-diacylglucosamine pyrophosphohydrase LpxH from Pseudomonas aeruginosa.
Crystal structures of the UDP-diacylglucosamine pyrophosphohydrase LpxH from Pseudomonas aeruginosa.
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铜绿假单胞菌 UDP-二酰基葡萄糖胺焦磷酸酶 LpxH 的晶体结构
DOI：
10.1038/srep32822
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发表时间：
2016-09-09
影响因子：
4.6
通讯作者：
Yao M
中科院分区：
文献类型：
--
作者：
Okada C;Wakabayashi H;Kobayashi M;Shinoda A;Tanaka I;Yao M
脂质A（也称为内毒素）是脂多糖的疏水部分。它是革兰氏阴性菌生存所需的基本膜组分。参与其生物合成的酶是开发新型抗生素的有吸引力的靶标。LpxH催化脂质A生物合成途径的第四步，并裂解UDP-2，3-二酰基葡糖胺的焦磷酸键，产生2，3-二酰基葡糖胺1-磷酸（脂质X）和UMP。在这里，我们提出的LpxH的结构从铜绿假单胞菌（PaLpxH）。PaLpxH由两个结构域组成：与金属磷酸酯酶同源的催化结构域和螺旋插入结构域。脂质X被捕获在这两个结构域之间的缝隙中，其磷酸基团面向双核金属（Mn 2+）中心，两个酰基链埋在疏水空腔中。的结构表明，一个大的构象变化发生在脂质X结合位点的表面上的产品分子的结合/释放。基于这些观察结果，我们提出了一种新的脂质X嵌入模型，该模型涉及螺旋α6的剪刀状运动，导致脂质X释放到脂质双层中。
Lipid A (also known as endotoxin) is the hydrophobic portion of lipopolysaccharides. It is an essential membrane component required for the viability of gram-negative bacteria. The enzymes involved in its biosynthesis are attractive targets for the development of novel antibiotics. LpxH catalyzes the fourth step of the lipid A biosynthesis pathway and cleaves the pyrophosphate bond of UDP-2,3-diacylglucosamine to yield 2,3-diacylglucosamine 1-phosphate (lipid X) and UMP. Here we present the structures of LpxH from Pseudomonas aeruginosa (PaLpxH). PaLpxH consists of two domains: a catalytic domain that is homologous to the metallophosphoesterases and a helical insertion domain. Lipid X was captured in the crevice between these two domains, with its phosphate group facing the dinuclear metal (Mn2+) center and two acyl chains buried in the hydrophobic cavity. The structures reveal that a large conformational change occurs at the lipid X binding site surface upon the binding/release of the product molecule. Based on these observations, we propose a novel model for lipid X embedding, which involves the scissor-like movement of helix α6, resulting in the release of lipid X into the lipid bilayer.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
15
作者：
Hoff, RH;Mertz, P;Hengge, AC
通讯作者：
Hengge, AC
影响因子：
5.4
作者：
Funhoff, EG;Wang, WL;Averill, BA
通讯作者：
Averill, BA
影响因子：
4.8
作者：
Babinski, KJ;Kanjilal, SJ;Raetz, CRH
通讯作者：
Raetz, CRH
影响因子：
4.8
作者：
Young, Hayley E.;Donohue, Matthew P.;Zhou, Pei
通讯作者：
Zhou, Pei