BACTERIAL CELL SURFACE STRUCTURE FUNCTIONS & BIOGENESIS

描述：(改编自调查人员摘要)快速 越来越多的细菌中的膜蛋白被发现 含有N-端脂氨基酸N-酰基-二甘油基半胱氨酸， 所有细菌脂蛋白的标志。截至1993年，超过130家 在革兰氏阳性菌和革兰氏阳性菌中都发现了脂蛋白 负性细菌覆盖了广泛的属和种。这个 细菌中脂蛋白的生物合成既是暂时的，也是 在空间上与这些膜蛋白的出口有关 细胞质膜。这些蛋白质是作为前体蛋白制成的。 具有N-末端信号序列，该信号序列在 信号序列和成熟蛋白的连接处。跟随 前体蛋白与出口机制的相互作用 由SecA、SecY、SecD和SecF蛋白定义，前脂蛋白是 胞质中的三种酶的修饰和加工 薄膜。这三种酶是前脂蛋白二酰甘油 转移酶、前脂蛋白信号肽和载脂蛋白N- 分别由LGT、LSP和LNT基因编码的酰基转移酶， 在大肠杆菌和鼠伤寒沙门氏菌中。在任何方面有缺陷的突变体 这三种基因都是有条件致命性的。此外，LNT突变体 也对铜敏感，LNT基因与可爱的等位基因 基因，六个基因之一，推测参与铜的运输和 在大肠杆菌中的动态平衡。 以大肠杆菌主要外膜脂蛋白为模型系统， 研究人员建议：(I)阐明生物化学基础 大肠杆菌中脂蛋白生物合成途径的本质 或鼠伤寒沙门氏菌；(Ii)鉴定编码基因 脂蛋白：在大肠杆菌中的肽聚糖连接酶；(Iii)研究 前脂蛋白修饰和组装的结构、功能和组装 加工酶；及(Iv)研究 载脂蛋白N-酰化与二价体的转运和动态平衡 阳离子，如大肠杆菌中的铜。拟议研究的结果 将提供有关结构、功能和 细菌中脂蛋白的生物发生。这些研究还将提供 寻找或设计抗菌剂的合理基础 利用这一途径的酶作为靶标。

DESCRIPTION: (adapted from investigator's abstract) A rapidly increasing number of membrane proteins in bacteria have been found to contain an N- terminal lipoamino acid, N-acyl-diacylglycerylcysteine, the hallmark of all bacterial lipoproteins. As of 1993, more than 130 lipoproteins have been identified in both gram positive and gram negative bacteria covering a wide spectrum of genera and species. The biosynthesis of lipoproteins in bacteria is both temporally and spatially related to the export of these membrane proteins across the cytoplasmic membranes. These proteins are made as precursor proteins with N-terminal signal sequences which contain a "lipobox" sequence at the junction of the signal sequences and the mature proteins. Following the interaction of the precursor proteins with the export machinery defined by the SecA, SecY SecD and SecF proteins, the prolipoproteins are modified and processed by three enzymes located in the cytoplasmic membrane. These three enzymes are prolipoprotein diacylglyceral transferase, prolipoprotein signal peptidase and apolipoprotein N- acyltransferase encoded by the lgt, lsp, and lnt genes, respectively, in Escherichia coli and Salmonella typhimurium. Mutants defective in any of these three genes are conditionally lethal. In addition, lnt mutants are also copper sensitive, and the lnt gene is allelic with the cutE gene, one of six genes postulated to be involved in copper transport and homeostasis in E. coli. Using the E. coli major outer membrane lipoprotein as the model system, the investigator proposes; (i) to elucidate the biochemical basis for the essential nature of the lipoprotein biosynthetic pathway in E. coli or S. typhimurium; (ii) to identify the gene encoding lipoprotein:peptidoglycan ligase in E. coli; (iii) to study the structure, function and assembly of the prolipoprotein modification and processing enzymes; and (iv) to study the interrelationship between apolipoprotein N-acylation and the transport and homeostasis of divalent cations such as Cu++ in E. coli. The results of the proposed studies will provide new information regarding the structures, functions and biogenesis of lipoproteins in bacteria. These studies will also provide a rational basis for the search or design of antibacterial agents which utilize the enzymes of this pathway as targets.