The first direct evaluation of the two-active site mechanism for chitin synthase.
The first direct evaluation of the two-active site mechanism for chitin synthase.
复制标题
首次直接评估几丁质合酶的双活性位点机制。
DOI：
10.1021/jo035100c
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Finney,NathanielS
中科院分区：
文献类型：
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作者：
Yeager,AdamR;Finney,NathanielS
几丁质合成酶聚合UDP-GlcNAc形成几丁质（poly-β(1,4)-GlcNAc），是真菌细胞壁生物合成所必需的。几丁质链中GlcNAc残基的交替取向导致了几丁质合成酶具有两个活性位点的提议。我们报告这种可能性的第一次直接试验的结果。两种简单的尿嘧啶衍生二聚体抑制剂显示出比单体对照大10倍的抑制作用，与两个活性位点的存在一致。这一发现对抗真菌药物的开发以及对糖基转移酶聚合的理解具有重要意义。
Chitin synthase polymerizes UDP-GlcNAc to form chitin (poly-β(1,4)-GlcNAc) and is essential for fungal cell wall biosynthesis. The alternating orientation of the GlcNAc residues within the chitin chain has led to the proposal that chitin synthase possesses two active sites. We report the results of the first direct test of this possibility. Two simple uridine-derived dimeric inhibitors are shown to exhibit 10-fold greater inhibition than a monomeric control, consistent with the presence of two active sites. This observation has important implications for the development of antifungal agents, as well as the understanding of polymerizing glycosyltransferases.