模块化非核糖体肽合成酶必要构象变化的结构洞察
Structural insight into the necessary conformational changes of modular nonribosomal peptide synthetases.
作者信息
Gulick Andrew M
机构信息
Hauptman-Woodward Medical Research Institute, Buffalo, NY, USA; Department of Structural Biology, University at Buffalo, Buffalo, NY, USA.
出版信息
Curr Opin Chem Biol. 2016 Dec;35:89-96. doi: 10.1016/j.cbpa.2016.09.005. Epub 2016 Sep 25.
Abstract
Nonribosomal peptide synthetases (NRPSs) catalyze the assembly line biosynthesis of peptide natural products that play important roles in microbial signaling and communication. These multidomain enzymes use an integrated carrier protein that delivers the growing peptide to the catalytic domains, requiring coordinated conformational changes that allow the proper sequence of synthetic steps. Recent structural studies of NRPSs have described important conformational states and illustrate the critical role of a small subdomain within the adenylation domains. This subdomain alternates between catalytic conformations and also serves as a linker domain, providing further conformational flexibility to enable the carrier to project from the core of NRPS. These studies are described along with remaining questions in the study of the structural dynamics of NRPSs.
摘要
非核糖体肽合成酶（NRPSs）催化肽类天然产物的流水线式生物合成，这些产物在微生物信号传导和交流中发挥着重要作用。这些多结构域酶使用一种整合的载体蛋白，将不断增长的肽传递到催化结构域，这需要协调的构象变化，以确保合成步骤的正确顺序。最近对NRPSs的结构研究描述了重要的构象状态，并阐明了腺苷化结构域内一个小亚结构域的关键作用。这个亚结构域在催化构象之间交替，还充当连接结构域，提供进一步的构象灵活性，使载体能够从NRPS的核心伸出。本文将介绍这些研究以及NRPSs结构动力学研究中仍存在的问题。
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