非核糖体肽合成酶环化结构域的动力学与机制阐释
Dynamics and mechanistic interpretations of nonribosomal peptide synthetase cyclization domains.
作者信息
Gnann Andrew D, Marincin Kenneth, Frueh Dominique P, Dowling Daniel P
机构信息
Department of Chemistry, University of Massachusetts Boston, Boston, MA, 02125, USA.
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
出版信息
Curr Opin Chem Biol. 2023 Feb;72:102228. doi: 10.1016/j.cbpa.2022.102228. Epub 2022 Nov 16.
Abstract
Ox-/thiazoline groups in nonribosomal peptides are formed by a variant of peptide-forming condensation domains called heterocyclization (Cy) domains and appear in a range of pharmaceutically important natural products and virulence factors. Recent cryo-EM, crystallographic, and NMR studies of Cy domains make it opportune to revisit outstanding questions regarding their molecular mechanisms. This review covers structural and dynamical findings about Cy domains that will inform future bioengineering efforts and our understanding of natural product synthesis.
摘要
非核糖体肽中的氧代/噻唑啉基团由一种称为杂环化（Cy）结构域的肽形成缩合结构域变体形成，并出现在一系列具有重要药学意义的天然产物和毒力因子中。最近对Cy结构域的冷冻电镜、晶体学和核磁共振研究使得重新审视关于其分子机制的悬而未决的问题成为契机。本综述涵盖了关于Cy结构域的结构和动力学研究结果，这些结果将为未来的生物工程努力以及我们对天然产物合成的理解提供信息。
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