The mechanism of action of ramoplanin and enduracidin
The mechanism of action of ramoplanin and enduracidin
复制标题
DOI：
10.1039/b515328j
复制
发表时间：
2006-01-01
影响因子：
--
通讯作者：
Walker, S
中科院分区：
文献类型：
--
作者：
Fang, X;Tiyanont, K;Walker, S
脂糖缩肽抗生素雷莫普拉宁被认为通过与成熟肽聚糖途径的中间产物沿着结合来抑制细菌细胞壁的生物合成，从而干扰进一步的酶促加工。两个连续的酶促步骤可以被雷莫拉宁阻断，但是关于其中一个步骤是否被优先抑制还没有明确的信息。在这里，我们使用抑制动力学和结合试验，以评估是否雷莫拉宁和相关化合物雷帕霉素有一个内在的偏好，一个步骤超过其他。与MurG步骤相比，雷莫拉宁和雷帕霉素都优先抑制肽聚糖生物合成的转糖基化步骤。较强抑制作用的基础是对转糖基酶底物脂质II的亲和力大于MurG底物脂质I。这些结果提供了令人信服的证据，雷莫拉宁和雷帕霉素的主要细胞靶点是肽聚糖生物合成的转糖基化步骤。
The lipoglycodepsipeptide antibiotic ramoplanin is proposed to inhibit bacterial cell wall biosynthesis by binding to intermediates along the pathway to mature peptidoglycan, which interferes with further enzymatic processing. Two sequential enzymatic steps can be blocked by ramoplanin, but there is no definitive information about whether one step is inhibited preferentially. Here we use inhibition kinetics and binding assays to assess whether ramoplanin and the related compound enduracidin have an intrinsic preference for one step over the other. Both ramoplanin and enduracidin preferentially inhibit the transglycosylation step of peptidoglycan biosynthesis compared with the MurG step. The basis for stronger inhibition is a greater affinity for the transglycosylase substrate Lipid II over the MurG substrate Lipid I. These results provide compelling evidence that ramoplanin's and enduracidin's primary cellular target is the transglycosylation step of peptidoglycan biosynthesis.