The direction of glycan chain elongation by peptidoglycan Glycosyltransferases
The direction of glycan chain elongation by peptidoglycan Glycosyltransferases
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DOI：
10.1021/ja075965y
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发表时间：
2007-10-24
影响因子：
15
通讯作者：
Walker, Suzanne
中科院分区：
文献类型：
--
作者：
Perlstein, Deborah L.;Zhang, Yi;Walker, Suzanne
肽聚糖糖基转移酶（pgt）是一种高度保守的酶，它催化脂质II聚合形成细菌蛋白的聚糖链。因为它们在细菌细胞壁合成中起着关键作用，这些酶是潜在的重要抗生素靶点；然而，它们的机制尚不清楚。关于这些酶的一个长期存在的问题是，它们是否通过在端粒（还原）端或4-羟基（非还原）端添加亚基来延长聚糖链。我们已经开发了一种方法来测试链延伸的方向，涉及使用在其非还原端被阻断的新生肽聚糖链。当金黄色葡萄球菌PBP2、风水球菌PBP1A、大肠杆菌PBP1A或大肠杆菌PBP1B的PGT结构域存在时，这些被阻断的底物与脂质II反应形成更长的聚糖链。这些结果表明，pgt通过在生长的聚合物的端粒（还原）端添加双糖亚基来延长新生的肽聚糖链。
Peptidoglycan glycosyltransferases (PGTs) are highly conserved enzymes that catalyze the polymerization of Lipid II to form the glycan strands of bacterial murein. Because they play a key role in bacterial cell wall synthesis, these enzymes are potentially important antibiotic targets; however, their mechanisms are not yet understood. One longstanding question about these enzymes is whether they elongate glycan chains by adding subunits to the anomeric (reducing) end or to the 4-hydroxyl (nonreducing) end. We have developed an approach to test the direction of chain elongation that involves the use of nascent peptidoglycan chains which are blocked at their nonreducing ends. In the presence of the PGT domains of Staphylococcus aureus PBP2, Aquifex aeolicus PBP1A, Escherichia coli PBP1A, or Escherichia coli PBP1B, these blocked substrates react with Lipid II to form longer glycan chains. These results establish that PGTs elongate nascent pepticloglycan chains by the addition of disaccharide subunits to the anomeric (reducing) end of the growing polymer.