Structural advances toward understanding the catalytic activity and conformational dynamics of modular nonribosomal peptide synthetases
文献信息
Ketan D. Patel, Monica R. MacDonald, Syed Fardin Ahmed, Jitendra Singh, Andrew M. Gulick
Covering: up to fall 2022. Nonribosomal peptide synthetases (NRPSs) are a family of modular, multidomain enzymes that catalyze the biosynthesis of important peptide natural products, including antibiotics, siderophores, and molecules with other biological activity. The NRPS architecture involves an assembly line strategy that tethers amino acid building blocks and the growing peptides to integrated carrier protein domains that migrate between different catalytic domains for peptide bond formation and other chemical modifications. Examination of the structures of individual domains and larger multidomain proteins has identified conserved conformational states within a single module that are adopted by NRPS modules to carry out a coordinated biosynthetic strategy that is shared by diverse systems. In contrast, interactions between modules are much more dynamic and do not yet suggest conserved conformational states between modules. Here we describe the structures of NRPS protein domains and modules and discuss the implications for future natural product discovery.
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来源期刊
Natural Product Reports
Natural Product Reports (NPR) is a critical review journal that stimulates progress in all areas of natural products research, including isolation, structural and stereochemical determination, biosynthesis, biological activity and synthesis. The scope of the journal is very broad, and many reviews discuss the role of natural products in the wider bioinorganic, bioorganic and chemical biology communities. Areas covered include the following: Enzymology Nucleic acids Genetics Chemical ecology Carbohydrates Primary and secondary metabolism Analytical techniques NPR articles are designed to give an interesting insight into the topic, focusing on the key developments that have shaped a field. Authors are encouraged to include their own perspective on developments, trends and future directions. Articles providing a very comprehensive overview or exhaustive list of previous literature and lacking critical insight are generally not suitable for publication in NPR. Meta-analyses of previously published data using existing tools can be included, however NPR articles should not include any new methods or data.
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