Department of Biochemistry, McGill University, Montréal, QC H3G 0B1, Canada.
Department of Biochemistry, McGill University, Montréal, QC H3G 0B1, Canada.
Curr Opin Struct Biol. 2018 Apr;49:104-113. doi: 10.1016/j.sbi.2018.01.011. Epub 2018 Feb 13.
Nonribosomal peptide synthetases (NRPSs) produce peptide products with wide-ranging biological activities. NRPSs are macromolecular machines with modular assembly-line logic, a complex catalytic cycle, moving parts and multiple active sites. They are organized into repeating sets of domains, called modules. Each module contains all functionality to introduce a building block into the growing peptide, many also perform cosynthetic tailoring. Structures of individual domains have provided insights into their catalytic mechanisms, but with one exception, larger NRPS proteins were refractory to structure determination. Recently, structure determination succeeded for four multi-domain NRPS proteins: an alternative formylating initiation and two termination modules as well as a large cross-module construct. This review highlights how these data, together with novel didomain structures, contribute to a holistic view of the architecture, domain-domain interactions and conformational changes in NRPS megaenzymes.
非核糖体肽合成酶（NRPSs）产生具有广泛生物活性的肽产物。NRPSs 是具有模块化装配线逻辑、复杂催化循环、可移动部件和多个活性位点的大分子机器。它们被组织成重复的结构域集，称为模块。每个模块都包含将构建块引入生长肽中的所有功能，许多模块还执行共合成修饰。单个结构域的结构提供了对其催化机制的深入了解，但有一个例外，较大的 NRPS 蛋白难以确定其结构。最近，四种多结构域 NRPS 蛋白的结构确定取得了成功：一种替代的甲酰化起始和两个终止模块以及一个大型跨模块构建体。本综述强调了这些数据以及新型双结构域结构如何为 NRPS 超级酶的架构、结构域-结构域相互作用和构象变化提供整体视图。
