White Stephen W, Zheng Jie, Zhang Yong-Mei
Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Annu Rev Biochem. 2005;74:791-831. doi: 10.1146/annurev.biochem.74.082803.133524.
The type II fatty acid synthetic pathway is the principal route for the production of membrane phospholipid acyl chains in bacteria and plants. The reaction sequence is carried out by a series of individual soluble proteins that are each encoded by a discrete gene, and the pathway intermediates are shuttled between the enzymes as thioesters of an acyl carrier protein. The Escherichia coli system is the paradigm for the study of this system, and high-resolution X-ray and/or NMR structures of representative members of every enzyme in the type II pathway are now available. The structural biology of these proteins reveals the specific three-dimensional features of the enzymes that explain substrate recognition, chain length specificity, and the catalytic mechanisms that define their roles in producing the multitude of products generated by the type II system. These structures are also a valuable resource to guide antibacterial drug discovery.
II型脂肪酸合成途径是细菌和植物中膜磷脂酰基链产生的主要途径。该反应序列由一系列各自由一个离散基因编码的单个可溶性蛋白质进行,并且途径中间体作为酰基载体蛋白的硫酯在酶之间穿梭。大肠杆菌系统是研究该系统的范例,现在II型途径中每种酶的代表性成员的高分辨率X射线和/或核磁共振结构都已可得。这些蛋白质的结构生物学揭示了酶的特定三维特征,这些特征解释了底物识别、链长特异性以及定义它们在产生II型系统产生的众多产物中所起作用的催化机制。这些结构也是指导抗菌药物发现的宝贵资源。