Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Early Discovery Biochemistry Department, Genentech Inc., South San Francisco, California 94114, United States.
J Am Chem Soc. 2020 Mar 18;142(11):5024-5028. doi: 10.1021/jacs.0c01576. Epub 2020 Mar 6.
PaaA is a RiPP enzyme that catalyzes the transformation of two glutamic acid residues within a substrate peptide into the bicyclic core of Pantocin A. Here, for the first time, we use mRNA display techniques to understand RiPP enzyme-substrate interactions to illuminate PaaA substrate recognition. Additionally, our data revealed insights into the enzymatic timing of glutamic acid modification. The technique developed is quite sensitive and a significant advancement over current RiPP studies and opens the door to enzyme modified mRNA display libraries for natural product-like inhibitor pans.
PaaA 是一种 RiPP 酶,可催化底物肽内的两个谷氨酸残基转化为 Pantocin A 的双环核心。在这里,我们首次使用 mRNA 显示技术来了解 RiPP 酶-底物相互作用,以阐明 PaaA 底物识别。此外,我们的数据还揭示了谷氨酸修饰的酶促时间的一些见解。所开发的技术非常灵敏,比当前的 RiPP 研究有了显著的进步,并为天然产物样抑制剂泛酶的酶修饰 mRNA 显示文库开辟了道路。