Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120, Heidelberg, Germany.
Department of Chemistry, Haverford College, Haverford, PA, 19041, USA.
Angew Chem Int Ed Engl. 2016 Aug 16;55(34):9834-40. doi: 10.1002/anie.201602614. Epub 2016 Jul 20.
The nonribosomal peptide synthetases (NRPSs) are one of the most promising resources for the production of new bioactive molecules. The mechanism of NRPS catalysis is based around sequential catalytic domains: these are organized into modules, where each module selects, modifies, and incorporates an amino acid into the growing peptide. The intermediates formed during NRPS catalysis are delivered between enzyme centers by peptidyl carrier protein (PCP) domains, which makes PCP interactions and movements crucial to NRPS mechanism. PCP movement has been linked to the domain alternation cycle of adenylation (A) domains, and recent complete NRPS module structures provide support for this hypothesis. However, it appears as though the A domain alternation alone is insufficient to account for the complete NRPS catalytic cycle and that the loaded state of the PCP must also play a role in choreographing catalysis in these complex and fascinating molecular machines.
非核糖体肽合成酶（NRPSs）是产生新生物活性分子的最有前途的资源之一。NRPS 催化的机制基于顺序催化结构域：这些结构域被组织成模块，其中每个模块选择、修饰和将氨基酸掺入到生长中的肽中。NRPS 催化过程中形成的中间体通过肽酰载体蛋白（PCP）结构域在酶中心之间传递，这使得 PCP 相互作用和运动对 NRPS 机制至关重要。PCP 运动与腺苷酰化（A）结构域的结构域交替循环有关，最近的完整 NRPS 模块结构为这一假设提供了支持。然而，似乎仅仅 A 结构域的交替不足以解释完整的 NRPS 催化循环，并且负载状态的 PCP 也必须在这些复杂而迷人的分子机器中发挥作用，以协调催化。
