The Glycosyltransferases of LPS Core: A Review of Four Heptosyltransferase Enzymes in Context.

The Glycosyltransferases of LPS Core: A Review of Four Heptosyltransferase Enzymes in Context.
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LPS 核心的糖基转移酶: 四种肽基转移酶的背景综述。

DOI:
10.3390/ijms18112256
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发表时间:
2017-10-27
影响因子:
5.6
通讯作者:
Taylor EA
Taylor EA
中科院分区:
生物学2区
文献类型:
--
作者:
Cote JM;Taylor EA

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细菌抗生素耐药性是当今世界上一个迅速扩大的问题。革兰氏阴性菌的外膜功能化提供了对细胞外抗菌素的保护,并作为先天耐药机制。脂多糖(LPS)是革兰氏阴性菌的主要细胞表面成分,有助于保护细菌免受细胞外威胁。脂多糖是通过一系列糖基转移酶(GTs)连续添加糖部分合成的。庚基转移酶催化多个庚糖的加入形成LPS的核心区域;在所有革兰氏阴性菌中最多发现四种庚基转移酶。这四种中研究最多的是HepI。缺乏HepI的细胞在其细胞表面显示截断的LPS,导致它们更容易受到疏水抗生素的影响。HepI-IV都是GT-B结构家族的结构相似的成员,这是一类被发现具有高度动态的酶。了解庚基转移酶的构象变化对有效抑制它们非常重要,同时也有助于了解所有的GT-B酶。寻找新的更智能的方法来抑制细菌生长是至关重要的,而Heptosyltransferases可能为如何抑制许多GT-B酶提供一个重要的模型。
Bacterial antibiotic resistance is a rapidly expanding problem in the world today. Functionalization of the outer membrane of Gram-negative bacteria provides protection from extracellular antimicrobials, and serves as an innate resistance mechanism. Lipopolysaccharides (LPS) are a major cell-surface component of Gram-negative bacteria that contribute to protecting the bacterium from extracellular threats. LPS is biosynthesized by the sequential addition of sugar moieties by a number of glycosyltransferases (GTs). Heptosyltransferases catalyze the addition of multiple heptose sugars to form the core region of LPS; there are at most four heptosyltransferases found in all Gram-negative bacteria. The most studied of the four is HepI. Cells deficient in HepI display a truncated LPS on their cell surface, causing them to be more susceptible to hydrophobic antibiotics. HepI–IV are all structurally similar members of the GT-B structural family, a class of enzymes that have been found to be highly dynamic. Understanding conformational changes of heptosyltransferases are important to efficiently inhibiting them, but also contributing to the understanding of all GT-B enzymes. Finding new and smarter methods to inhibit bacterial growth is crucial, and the Heptosyltransferases may provide an important model for how to inhibit many GT-B enzymes.
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