Exploring the Post-translational Enzymology of PaaA by mRNA Display

被引：34
作者：
Fleming, Steven R. [1 ]
Himes, Paul M. [1 ]
Ghodge, Swapnil, V [1 ,2 ]
Goto, Yuki [3 ,4 ]
Suga, Hiroaki [3 ,5 ]
Bowers, Albert A. [1 ]
机构：
[1] Univ N Carolina, Div Chem Biol & Med Chem, UNC Eshelman Sch Pharm, Chapel Hill, NC 27599 USA
[2] Genentech Inc, Early Discovery Biochem Dept, San Francisco, CA 94114 USA
[3] Univ Tokyo, Grad Sch Sci, Dept Chem, Tokyo 1130033, Japan
[4] JST, PRESTO, Tokyo 1130033, Japan
[5] JST, CREST, Tokyo 1130033, Japan
来源：
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2020年 / 142卷 / 11期
关键词：
PHAGE; BIOSYNTHESIS; SELECTION; IDENTIFICATION; SEQUENCES; PEPTIDES; INSIGHTS;
D O I：
10.1021/jacs.0c01576
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
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.
引用
收藏
页码：5024 / 5028
页数：5
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