Helm Jeremiah S, Chen Lan, Walker Suzanne
Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
J Am Chem Soc. 2002 Nov 27;124(47):13970-1. doi: 10.1021/ja021097n.
Ramoplanin is a cyclicdepsipeptide antibiotic that inhibits peptidoglycan biosynthesis. It was proposed in 1990 to block the MurG step of peptidoglycan synthesis by binding to the substrate of MurG, Lipid I. The proposed mechanism of MurG inhibition has become widely accepted even though it was never directly tested. In this paper, we disprove the accepted mechanism for how ramoplanin functions, and we present an alternative mechanism. This work has implications for the design of ramoplanin derivatives and may influence how other proposed substrate binding antibiotics are studied.
瑞莫拉宁是一种抑制肽聚糖生物合成的环脂肽抗生素。1990年有人提出，它通过与MurG的底物脂质I结合来阻断肽聚糖合成的MurG步骤。尽管从未直接进行过测试，但MurG抑制的这一提出的机制已被广泛接受。在本文中，我们反驳了关于瑞莫拉宁作用方式的公认机制，并提出了另一种机制。这项工作对瑞莫拉宁衍生物的设计有影响，可能会影响对其他提出的底物结合抗生素的研究方式。
