衣霉素、脂多霉素B和多醚霉素A的作用模式：抑制大肠杆菌的磷酸-N-乙酰胞壁酰-五肽转位酶
Modes of action of tunicamycin, liposidomycin B, and mureidomycin A: inhibition of phospho-N-acetylmuramyl-pentapeptide translocase from Escherichia coli.
作者信息
Brandish P E, Kimura K I, Inukai M, Southgate R, Lonsdale J T, Bugg T D
机构信息
Department of Chemistry, University of Southampton, Highfield, United Kingdom.
出版信息
Antimicrob Agents Chemother. 1996 Jul;40(7):1640-4. doi: 10.1128/AAC.40.7.1640.
Abstract
Using a continuous fluorescence-based enzyme assay, we have characterized the antibacterial agents tumicamycin and liposidomycin B as inhibitors of solubilized Escherichia coli phospho-N-acetylmuramyl-pentapeptide translocase. Tunicamycin exhibited reversible inhibition (Ki = 0.55 +/- 0.1 microM) which was noncompetitive with respect to the lipid acceptor substrate and competitive with respect to the fluorescent substrate analog, dansyl-UDPMurNAc-pentapeptide. Liposidomycin B exhibited slow-binding inhibition (Ki = 80 +/- 15 nM) which was competitive with respect to the lipid acceptor substrate and noncompetitive with respect to dansyl-UDPMurNAc-pentapeptide. These results provide insight into the molecular mechanisms of action of these two classes of nucleoside antibiotics.
摘要
通过基于连续荧光的酶分析，我们已将抗细菌剂衣霉素和脂多霉素B表征为溶解的大肠杆菌磷酸-N-乙酰胞壁酰-五肽转位酶的抑制剂。衣霉素表现出可逆抑制作用（Ki = 0.55±0.1 microM），相对于脂质受体底物而言是非竞争性的，而相对于荧光底物类似物丹磺酰-UDPMurNAc-五肽而言是竞争性的。脂多霉素B表现出慢结合抑制作用（Ki = 80±15 nM），相对于脂质受体底物而言是竞争性的，而相对于丹磺酰-UDPMurNAc-五肽而言是非竞争性的。这些结果为这两类核苷抗生素的分子作用机制提供了深入了解。
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